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href="https://guadalajara.academia.edu/RobertoFloresMoreno">Roberto Flores-Moreno</a><p class="suggested-user-card__user-info__subheader ds2-5-body-xs">Universidad de Guadalajara</p></div></div><div class="suggested-user-card"><div class="suggested-user-card__avatar social-profile-avatar-container"><a href="https://karachi.academia.edu/SalmanAhmed"><img class="profile-avatar u-positionAbsolute" alt="Salman Ahmed" border="0" onerror="if (this.src != '//a.academia-assets.com/images/s200_no_pic.png') this.src = '//a.academia-assets.com/images/s200_no_pic.png';" width="200" height="200" src="https://0.academia-photos.com/3280636/1088397/163865009/s200_salman.ahmed.jpg" /></a></div><div class="suggested-user-card__user-info"><a class="suggested-user-card__user-info__header ds2-5-body-sm-bold ds2-5-body-link" href="https://karachi.academia.edu/SalmanAhmed">Salman Ahmed</a><p class="suggested-user-card__user-info__subheader ds2-5-body-xs">University of Karachi</p></div></div><div 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class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Nai-Kong Cheung</h3></div><div class="js-work-strip profile--work_container" data-work-id="127783960"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/127783960/Desensitizing_the_autonomic_nervous_system_to_mitigate_anti_GD2_monoclonal_antibody_side_effects"><img alt="Research paper thumbnail of Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects" class="work-thumbnail" src="https://attachments.academia-assets.com/121466781/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/127783960/Desensitizing_the_autonomic_nervous_system_to_mitigate_anti_GD2_monoclonal_antibody_side_effects">Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects</a></div><div class="wp-workCard_item"><span>Frontiers in oncology</span><span>, May 15, 2024</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of p...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs. Methods: Through confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested. Results: Through confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational superresolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f03d7c1b069f22f24d9dc3904cd0d531" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":121466781,"asset_id":127783960,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/121466781/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="127783960"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="127783960"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 127783960; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="121197500"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/121197500/Bispecific_antibody_does_not_induce_T_cell_death_mediated_by_chimeric_antigen_receptor_against_disialoganglioside_GD2"><img alt="Research paper thumbnail of Bispecific antibody does not induce T-cell death mediated by chimeric antigen receptor against disialoganglioside GD2" class="work-thumbnail" src="https://attachments.academia-assets.com/116141120/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/121197500/Bispecific_antibody_does_not_induce_T_cell_death_mediated_by_chimeric_antigen_receptor_against_disialoganglioside_GD2">Bispecific antibody does not induce T-cell death mediated by chimeric antigen receptor against disialoganglioside GD2</a></div><div class="wp-workCard_item"><span>OncoImmunology</span><span>, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy approaches for retargeting lymphocytes toward cancer cells. Despite their success in lymphoblastic leukemia, solid tumors have been more recalcitrant. Identifying therapeutic barriers facing CARmodified (CART) or BsAb-redirected T (BsAb-T) cells should facilitate their clinical translation to solid tumors. Novel lentiviral vectors containing low-affinity or high-affinity 4-1BB second-generation anti-GD2 (disialoganglioside) CARs were built to achieve efficient T cell transduction. The humanized anti-GD2 £ CD3 BsAb using the IgG-scFv platform was described previously. CART and BsAbengaged T cells were tested for viability, proliferation, and activation/exhaustion marker expression, and in vitro cytotoxicity against GD2(C) tumor cells. The antitumor effect of CAR-grafted and BsAb-T cells was compared in a human melanoma xenograft model. The majority of high CAR density T cells were depleted upon exposure to GD2(C) target cells while the BsAb-T cells survived. The in vitro cytotoxicity of the surviving CART cells was inferior to that of the BsAb-T cells. Using lowaffinity CARs, inclusion of the 4-1BB co-stimulatory domain or exclusion of a co-stimulatory domain, or blocking PD1 did not prevent CART cell depletion. Both CART cells and BsAb-T cells penetrated established subcutaneous human melanoma xenografts; while both induced tumor regression, BsAb was more efficient. The fate of T cells activated by BsAb differs substantially from that by CAR, translating into a more robust antitumor effect both in vitro and in vivo.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="10918f5cb33cf880f3e3e5db6ba8aa25" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":116141120,"asset_id":121197500,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/116141120/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="121197500"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="121197500"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 121197500; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=121197500]").text(description); $(".js-view-count[data-work-id=121197500]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 121197500; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='121197500']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "10918f5cb33cf880f3e3e5db6ba8aa25" } } $('.js-work-strip[data-work-id=121197500]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":121197500,"title":"Bispecific antibody does not induce T-cell death mediated by chimeric antigen receptor against disialoganglioside GD2","internal_url":"https://www.academia.edu/121197500/Bispecific_antibody_does_not_induce_T_cell_death_mediated_by_chimeric_antigen_receptor_against_disialoganglioside_GD2","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":116141120,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/116141120/thumbnails/1.jpg","file_name":"pmc5486173.pdf","download_url":"https://www.academia.edu/attachments/116141120/download_file","bulk_download_file_name":"Bispecific_antibody_does_not_induce_T_ce.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/116141120/pmc5486173-libre.pdf?1718739976=\u0026response-content-disposition=attachment%3B+filename%3DBispecific_antibody_does_not_induce_T_ce.pdf\u0026Expires=1740537265\u0026Signature=Sk8nTdJ5XF77-Z~Cdr3xJvm1cLsuliFBlPFcTIsUULypj33z629UI3rESDhfz1aMlboZxm67rmXmrxlCn0yoEXEd~63-9qYsCI1hFzA7aEv9gaJoN48cUNn3ujlthQH-KoRm1t9zx0a~uZb401M6GYmIPGJ7bgJ646-mLS0uHJkh8XSPead9Tf-Qof3uN8Oz-n7yVFordF46GWBGyJzx37uwHTxqgmYiX4bFRPyeLuwA0G3FzFf7FedNzTNF6XAAlUJy1q-IFyN6J89BGnbdJwa0XOhUi~qckLndWx2uNeKVXtl3HcbDyKnQssixjsbMlR7duHhSj6CMUG~to8GNMA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="117044641"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/117044641/Assessing_telomeric_DNA_content_in_pediatric_cancers_using_whole_genome_sequencing_data"><img alt="Research paper thumbnail of Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data" class="work-thumbnail" src="https://attachments.academia-assets.com/113008764/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/117044641/Assessing_telomeric_DNA_content_in_pediatric_cancers_using_whole_genome_sequencing_data">Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data</a></div><div class="wp-workCard_item"><span>Genome Biology</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background: Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background: Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers. Results: To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations. Conclusions: Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="81434565fdc024a7dd9f34458110e6c5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113008764,"asset_id":117044641,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113008764/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="117044641"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="117044641"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 117044641; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=117044641]").text(description); $(".js-view-count[data-work-id=117044641]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 117044641; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='117044641']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "81434565fdc024a7dd9f34458110e6c5" } } $('.js-work-strip[data-work-id=117044641]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":117044641,"title":"Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data","internal_url":"https://www.academia.edu/117044641/Assessing_telomeric_DNA_content_in_pediatric_cancers_using_whole_genome_sequencing_data","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":113008764,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/113008764/thumbnails/1.jpg","file_name":"pmc3580411.pdf","download_url":"https://www.academia.edu/attachments/113008764/download_file","bulk_download_file_name":"Assessing_telomeric_DNA_content_in_pedia.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/113008764/pmc3580411-libre.pdf?1712198864=\u0026response-content-disposition=attachment%3B+filename%3DAssessing_telomeric_DNA_content_in_pedia.pdf\u0026Expires=1740537266\u0026Signature=Wugr8mkZW7wvQr-S2AxwYcZyBSLrNyjdK06p2a51HdBTniL9zmds9UxkSTChyi7zfhu6judGqHO9Rvy6u4KlSoXfK7rGk290~YOCjp2Pp3BWXULqx6jZnDBydVY-znWTE692MOOzLJE-4jFV87IhWIWWEdHAiDQHObVC8hs7l1HnhvpXzRNrEdUqvfn8nBozJ9-xgGp7migjSWB-5omeOOnm8Bqp1c0oUyzMIaGrHYF5FA2rDM1XVlu4uTbUcH6lvPmfi92sa0iN4xsJhky0zsCGz~ohEOiWcIz-rKsZ7fCwPn81gWnq8DKn-i9GPSzW771t6Shc8B5yW6BY4Wvp-Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="102746915"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/102746915/GD2_targeted_immunotherapy_and_radioimmunotherapy"><img alt="Research paper thumbnail of GD2-targeted immunotherapy and radioimmunotherapy" class="work-thumbnail" src="https://attachments.academia-assets.com/102934372/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/102746915/GD2_targeted_immunotherapy_and_radioimmunotherapy">GD2-targeted immunotherapy and radioimmunotherapy</a></div><div class="wp-workCard_item"><span>Seminars in oncology</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Ganglioside GD2 is a tumor-associated surface antigen found in a broad spectrum of human cancers ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Ganglioside GD2 is a tumor-associated surface antigen found in a broad spectrum of human cancers and stem cells. They include pediatric embryonal tumors (neuroblastoma, retinoblastoma, brain tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma), as well as adult cancers (small cell lung cancer, melanoma, soft tissue sarcomas). Because of its restricted normal tissue distribution, GD2 has been proven safe for antibody targeting. Anti-GD2 antibody is now incorporated into the standard of care for the treatment of high-risk metastatic neuroblastoma. Building on this experience, novel combinations of antibodies, cytokines, cells, and genetically engineered products all directed at GD2 are rapidly moving into the clinic. In this review, past and present immunotherapy trials directed at GD2 will be summarized, highlighting the lessons learned and the future directions.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="634dcc42ad50c0ac8d89032c0096e53d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":102934372,"asset_id":102746915,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/102934372/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="102746915"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="102746915"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 102746915; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265549"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265549/Phase_I_Trial_of_Oral_Yeast_Derived_%CE%B2_Glucan_to_Enhance_Anti_GD2_Immunotherapy_of_Resistant_High_Risk_Neuroblastoma"><img alt="Research paper thumbnail of Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma" class="work-thumbnail" src="https://attachments.academia-assets.com/95319686/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265549/Phase_I_Trial_of_Oral_Yeast_Derived_%CE%B2_Glucan_to_Enhance_Anti_GD2_Immunotherapy_of_Resistant_High_Risk_Neuroblastoma">Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma</a></div><div class="wp-workCard_item"><span>Cancers</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance ant...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of complement-activating monoclonal antibodies. We conducted a phase I study (clinicaltrials.gov NCT00492167) to determine the safety of the combination of yeast-derived beta glucan (BG) and anti-GD2 murine monoclonal antibody 3F8 in patients with relapsed or refractory high-risk neuroblastoma. Patients received intravenous 3F8 (fixed dose of 10 mg/m2/day × 10 days) and oral BG (dose-escalated from 10–200 mg/kg/day × 17 days in cohorts of 3–6 patients each). Forty-four patients completed 141 cycles. One patient developed DLT: transient self-limiting hepatic transaminase elevation 5 days after starting BG (120 mg/kg/day). Overall, 1, 3, 12 and 24 evaluable patients had complete response, partial response, stable and progressive disease, respectively, at the end of treatment. Positive human anti-mouse antibody response and dectin-1 rs3901533 polymorphism were associate...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="be92aa188dcbbfedd2b1a8cf129a67ed" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319686,"asset_id":92265549,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319686/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265549"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265549"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265549; 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</script> <div class="js-work-strip profile--work_container" data-work-id="92265546"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265546/Influence_of_Fc_Modifications_and_IgG_Subclass_on_Biodistribution_of_Humanized_Antibodies_Targeting_L1CAM"><img alt="Research paper thumbnail of Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM" class="work-thumbnail" src="https://attachments.academia-assets.com/95319771/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265546/Influence_of_Fc_Modifications_and_IgG_Subclass_on_Biodistribution_of_Humanized_Antibodies_Targeting_L1CAM">Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM</a></div><div class="wp-workCard_item"><span>Journal of Nuclear Medicine</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Immuno-PET is a powerful tool to noninvasively characterize the in vivo biodistribution of engine...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Immuno-PET is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies. Methods: L1 cell adhesion molecule-targeting humanized (HuE71) IgG 1 and IgG 4 antibodies bearing identical variable heavy-and light-chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with 89 Zr, and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results: In addition to showing uptake in L1 cell adhesion molecule-expressing SKOV3 tumors, as does its parental counterpart HuE71 IgG 1 , the afucosylated variant having enhanced Fc-receptor affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG 1 with abrogated Fc-receptor binding did not show lymphoid uptake. The use of the IgG 4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline in the hinge region of the IgG 4 antibody to mitigate in vivo fragment antigen-binding arm exchange. Conclusion: Our findings highlight the influence of Fc modifications and the choice of IgG subclass on the in vivo biodistribution of antibodies and the potential outcomes thereof.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f388eeb727f08ebbccf84a2b38887fe1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319771,"asset_id":92265546,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319771/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265546"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265546"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265546; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265546]").text(description); $(".js-view-count[data-work-id=92265546]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265546; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265546']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f388eeb727f08ebbccf84a2b38887fe1" } } $('.js-work-strip[data-work-id=92265546]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265546,"title":"Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM","internal_url":"https://www.academia.edu/92265546/Influence_of_Fc_Modifications_and_IgG_Subclass_on_Biodistribution_of_Humanized_Antibodies_Targeting_L1CAM","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319771,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319771/thumbnails/1.jpg","file_name":"629.full.pdf","download_url":"https://www.academia.edu/attachments/95319771/download_file","bulk_download_file_name":"Influence_of_Fc_Modifications_and_IgG_Su.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319771/629.full-libre.pdf?1670302838=\u0026response-content-disposition=attachment%3B+filename%3DInfluence_of_Fc_Modifications_and_IgG_Su.pdf\u0026Expires=1740537266\u0026Signature=CFTEyLbPAiJCwa~VoCp7k-zqr5S2Z4evkj9vD5vPsRJCN7F8p8qYsQXiDxUhVlVHykPMqMAcfe1yfPEzCB9DGMWJ8sKjdqLgzSoXKdk7TQAdmkVMHWX3SFDnbAD2Nj9E5JDjOyPuqMXcsPqvDj1CStiRXd5WyPc2Xb~RO~wvjfVEtLf3xjQMWDcJkZQ1jURtb~5WPjyROQ8dQXRQT~YakcJ2hNkX8XbAZwXoeXzuPJQs9YhSTpJ~uCYDs6K~uKzp-M8eSNBEtwGgkUFefqGO-vhORHb6hnCBWQMCsuwpMAH4Vtf5o3vp~TfzFoA9Iyd23svmT1uT0nfIgcMH2po6Zg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265545"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265545/Posterior_reversible_encephalopathy_syndrome_in_neuroblastoma_patients_receiving_anti_GD23F8_monoclonal_antibody"><img alt="Research paper thumbnail of Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD23F8 monoclonal antibody" class="work-thumbnail" src="https://attachments.academia-assets.com/95319681/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265545/Posterior_reversible_encephalopathy_syndrome_in_neuroblastoma_patients_receiving_anti_GD23F8_monoclonal_antibody">Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD23F8 monoclonal antibody</a></div><div class="wp-workCard_item"><span>Cancer</span><span>, Apr 30, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background-Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background-Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic findings with rapid onset and potentially dire consequences. Patients experience hypertension, seizures, headache, visual disturbance, and/or altered mentation. Magnetic resonance imaging shows edematous changes in brain (especially parietal and occipital lobes). We report PRES associated with anti-G D2 monoclonal antibody (MoAb) immunotherapy which is now standard for high-risk neuroblastoma but has not previously been implicated in PRES. Methods-Successive clinical trials using the anti-G D2 MoAb 3F8 for neuroblastoma patients involved multiple cycles of standard-dose 3F8 (SD-3F8) (20 mg/m 2 /day, x5 days/cycle) or two cycles of high-dose 3F8 (HD-3F8) (80 mg/m 2 /day, x5 days/cycle) followed by cycles of SD-3F8. Results-PRES was diagnosed in 5/215 (2.3%) patients, including 3/160 (1.9%) patients receiving SD-3F8 and 2/55 (3.6%) patients receiving HD-3F8 (p=0.6). All five patients had a rapid return to clinical-radiologic baseline. PRES occurred in 3/26 (11.5%) patients whose prior</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="7dae1d155c098a5f79a8a00ae0584169" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319681,"asset_id":92265545,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319681/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265545"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265545"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265545; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265544"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/92265544/T_Cell_Mediated_Suppression_to_the_Terpolymer_poly_Glu_Lys_Phe_n_"><img alt="Research paper thumbnail of T-Cell-Mediated Suppression to the Terpolymer poly-(Glu, Lys, Phe)n*" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/92265544/T_Cell_Mediated_Suppression_to_the_Terpolymer_poly_Glu_Lys_Phe_n_">T-Cell-Mediated Suppression to the Terpolymer poly-(Glu, Lys, Phe)n*</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Intravenous injection of hapten-conjugated syngeneic cells results in specific immunological tole...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Intravenous injection of hapten-conjugated syngeneic cells results in specific immunological tolerance affecting both hapten-specific contact sensitivity and plaqueforming cell responses (1-4). Although the underlying basis for this nonresponsiveness is not fully understood, it appears that both the T- and B-cell compartments may be affected (3-5). In addition, several studies have reported the generation of specific suppressor T cells under these conditions (4-6). The antigen that was used to induce specific nonresponsiveness (suppression) in these studies was the synthetic linear polypeptide of L-glutamic acid, L-lysine and L-phenylalanine (GLO). 1 This antigen was chosen for several reasons. (a) The immune response to GL4 is under histocompatibility-linked immune response gene control (7). (b) Although previous attempts to identify GLO specific suppressor T cells in nonresponder mice have been unsuccessful (8, 9), we questioned whether induction with antigen-modified syngeneic ce...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265544"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265544"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265544; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265540"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/92265540/Procedes_pour_la_detection_de_maladie_residuelle_minimale"><img alt="Research paper thumbnail of Procedes pour la detection de maladie residuelle minimale" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/92265540/Procedes_pour_la_detection_de_maladie_residuelle_minimale">Procedes pour la detection de maladie residuelle minimale</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">La presente invention a trait a des procedes et des compositions pour l&#39;identification de mar...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">La presente invention a trait a des procedes et des compositions pour l&#39;identification de marqueurs de maladie residuelle minimale, ainsi qu&#39;a des marqueurs de cellules metastatiques. La presente invention a egalement trait a des procedes pour la detection de maladie residuelle minimale et de cellule metastatique chez un sujet.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265540"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265540"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265540; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265540]").text(description); $(".js-view-count[data-work-id=92265540]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265540; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265540']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=92265540]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265540,"title":"Procedes pour la detection de maladie residuelle minimale","internal_url":"https://www.academia.edu/92265540/Procedes_pour_la_detection_de_maladie_residuelle_minimale","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265539"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265539/Immunotherapy_and_Radioimmunotherapy_for_Desmoplastic_Small_Round_Cell_Tumor"><img alt="Research paper thumbnail of Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor" class="work-thumbnail" src="https://attachments.academia-assets.com/95319774/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265539/Immunotherapy_and_Radioimmunotherapy_for_Desmoplastic_Small_Round_Cell_Tumor">Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor</a></div><div class="wp-workCard_item"><span>Frontiers in Oncology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primari...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primarily affects adolescent and young adult males. The 5-year survival rate is 15-30% and few curative treatment options exist. Although there is no standard treatment for DSRCT, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of PDGFA and IGF-1R, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. As in cancer in general, interest in immunotherapy to treat DSRCT has increased in recent years. To that end, several types of immunotherapy are now being tested clinically, including monoclonal antibodies, radionuclide-conjugated antibodies, chimeric antigen receptor T cells, checkpoint inhibitors, and bispecific antibodies (BsAbs). These types of therapies may be particularly useful in DSRCT, which is frequently characterized by widespread intraperitoneal implants, which are di...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="df055a20f72bfe9a9bb8ffa029b87cdb" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319774,"asset_id":92265539,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319774/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265539"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265539"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265539; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265539]").text(description); $(".js-view-count[data-work-id=92265539]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265539; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265539']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "df055a20f72bfe9a9bb8ffa029b87cdb" } } $('.js-work-strip[data-work-id=92265539]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265539,"title":"Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor","internal_url":"https://www.academia.edu/92265539/Immunotherapy_and_Radioimmunotherapy_for_Desmoplastic_Small_Round_Cell_Tumor","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319774,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319774/thumbnails/1.jpg","file_name":"pdf.pdf","download_url":"https://www.academia.edu/attachments/95319774/download_file","bulk_download_file_name":"Immunotherapy_and_Radioimmunotherapy_for.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319774/pdf-libre.pdf?1670302836=\u0026response-content-disposition=attachment%3B+filename%3DImmunotherapy_and_Radioimmunotherapy_for.pdf\u0026Expires=1740537266\u0026Signature=W1cFhYxip2WS8zHN3WYLDqIlAmNfcXTr9chqYIQmp83Vq3cOLWBdKDpA5rKwEVM~y3prCqWBP~G4cJS8iZMdeb3kyo~Edvmp7P5WKzKW4QaJorpvSXahEdsAcKhfCe0Uz7vGx-0yGyqow-uALIkocMUU~wdwHzCWn1gEDmIV3p8Sfym80dD7ZLRdKBj~ZPIfgs7YSD2FIdsBw4Z7OBI3bo1rk-rgxe1Kjhs2zok2ApYoSxTHigavCOMkv7NBwqykizu2MWGSTvYvrKZ0s7Ne89LXK5Xrwz0l9ToJVhTX286IVPzOhKSbPnec8NMg1xNenD0Mj19fFBvvrFT3azpXeQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265538"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265538/Modulating_tumor_infiltrating_myeloid_cells_to_enhance_bispecific_antibody_driven_T_cell_infiltration_and_anti_tumor_response"><img alt="Research paper thumbnail of Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response" class="work-thumbnail" src="https://attachments.academia-assets.com/95319680/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265538/Modulating_tumor_infiltrating_myeloid_cells_to_enhance_bispecific_antibody_driven_T_cell_infiltration_and_anti_tumor_response">Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response</a></div><div class="wp-workCard_item"><span>Journal of Hematology &amp; Oncology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background Tumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesi...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background Tumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesis, growth, proliferation, and metastasis, while derailing the host anti-tumor response. TME impedes bispecific antibody (BsAb) or chimeric antigen receptor (CAR)-driven T cells infiltration, survival, and cytotoxic efficacy. Modulating tumor infiltrating myeloid cells (TIMs) could potentially improve the efficacy of BsAb. Methods We evaluated the effects of TIM modulation on BsAb-driven T cell infiltration into tumors, their persistence, and in vivo anti-tumor response. Anti-GD2 BsAb and anti-HER2 BsAb built on IgG-[L]-scFv platform were tested against human cancer xenografts in BALB-Rag2−/−IL-2R-γc-KO (BRG) mice. Depleting antibodies specific for polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic MDSC (M-MDSC), and tumor associated macrophage (TAM) were used to study the role of each TIM component. Dexamethasone, an established anti-inflammatory agent, was tested fo...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e5e2581022da58f642d6c34234939fbf" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319680,"asset_id":92265538,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319680/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265538"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265538"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265538; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265538]").text(description); $(".js-view-count[data-work-id=92265538]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265538; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265538']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265537"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/92265537/Expression_Analysis_of_GD2_by_Immunohistochemistry_in_Invasive_Breast_Carcinoma"><img alt="Research paper thumbnail of Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/92265537/Expression_Analysis_of_GD2_by_Immunohistochemistry_in_Invasive_Breast_Carcinoma">Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma</a></div><div class="wp-workCard_item"><span>Applied Immunohistochemistry & Molecular Morphology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The glycosphingolipid disialoganglioside GD2 is a cell surface-associated antigen expressed on tu...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The glycosphingolipid disialoganglioside GD2 is a cell surface-associated antigen expressed on tumors of neuroectodermal origin that serves as a target of immunotherapy in select cancer types. Information about the expression of GD2 in breast cancer is limited. In the present study, we investigate the utility of GD2 as a potential biomarker for targeted treatment. The study cohort consists of 386 breast carcinomas of several histologic types. GD2 expression was assessed in both whole tumor sections and tissue microarrays with anti-GD2 3F8 monoclonal antibody immunohistochemistry and correlated with clinicopathologic features and survival outcomes. A total of 134 (35%) breast carcinomas were positive for GD2, with a median H-score of 100. 3F8 staining displayed granular and predominantly cytoplasmic or perinuclear patterns, which was confined to the neoplastic tissue in nearly all cases. GD2 positivity was significantly associated with tumor histologic type (P=0.0015), low grade (P&lt;0.0001), estrogen receptor positivity (P&lt;0.0001), low stage (P=0.0014), and multifocality (P=0.022). Event-free survival and overall survival of patients with GD2-positive and GD2-negative tumors were not significantly different. Our results support further assessment of GD2 using the 3F8 antibody as a predictive and prognostic biomarker in breast cancer.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265537"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265537"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265537; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265537]").text(description); $(".js-view-count[data-work-id=92265537]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265537; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265537']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=92265537]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265537,"title":"Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma","internal_url":"https://www.academia.edu/92265537/Expression_Analysis_of_GD2_by_Immunohistochemistry_in_Invasive_Breast_Carcinoma","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265536"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265536/Reciprocal_impacts_of_telomerase_activity_and_tumor_cell_differentiation_in_neuroblastoma_tumor_biology"><img alt="Research paper thumbnail of Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology" class="work-thumbnail" src="https://attachments.academia-assets.com/95319766/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265536/Reciprocal_impacts_of_telomerase_activity_and_tumor_cell_differentiation_in_neuroblastoma_tumor_biology">Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Telomere maintenance and tumor cell differentiation have been separately implicated in neuroblast...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Telomere maintenance and tumor cell differentiation have been separately implicated in neuroblastoma malignancy. Their mechanistic connection is unclear. We analyzed neuroblastoma cell lines and morphologic subclones representing the adrenergic (ADRN) and mesenchymal (MES) differentiation states and uncovered sharp differences in their telomere protein and telomerase activity levels. Pharmacologic conversion of ADRN into MES cells elicited consistent and robust changes in the expression of telomere-related proteins. Conversely, stringent down-regulation of telomerase activity triggers the differentiation of ADRN into MES cells, which was reversible upon telomerase upregulation. Interestingly, the MES differentiation state is associated with elevated levels of innate immunity factors, including key components of the DNA-sensing pathway. Accordingly, MES but not ADRN cells can mount a robust response to viral infections in vitro. A gene expression signature based on telomere and cell ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="29c67e2c421cfbfedcd8b30b08a290f8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319766,"asset_id":92265536,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319766/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265536"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265536"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265536; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265536]").text(description); $(".js-view-count[data-work-id=92265536]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265536; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265536']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "29c67e2c421cfbfedcd8b30b08a290f8" } } $('.js-work-strip[data-work-id=92265536]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265536,"title":"Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology","internal_url":"https://www.academia.edu/92265536/Reciprocal_impacts_of_telomerase_activity_and_tumor_cell_differentiation_in_neuroblastoma_tumor_biology","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319766,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319766/thumbnails/1.jpg","file_name":"2021.05.09.442765.full.pdf","download_url":"https://www.academia.edu/attachments/95319766/download_file","bulk_download_file_name":"Reciprocal_impacts_of_telomerase_activit.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319766/2021.05.09.442765.full-libre.pdf?1670302858=\u0026response-content-disposition=attachment%3B+filename%3DReciprocal_impacts_of_telomerase_activit.pdf\u0026Expires=1740537266\u0026Signature=YwGRhjaeJZ9kM-q76BQtuF8YpfremF84WChU1BxX~xGOsD9iGFRkuNNcATL4CABuhUBXp~zKwb2uxaHpJ8g2-SH8fxtbeEei3vvb7eOgosvDesNiE~Lm2a0xMItZobd2uIeslvQIQU6By55qrfYftS20srumzMjWWJ8RdjgwhAYZmWCAyqHlS~l9gbUokHlSVpD26oQd6ZtLo34dtPZ-Jl3I4rb8X3Xn7Lt1z1ck~xIjXoZkPmANPQsodF6oNwLqdKjiSvRNgghOD3WIhQWUXQEj~5sb3WdFJjzsyICmKaBP6iJrGFNFl3sFGyowUfmEdTsN6~gpolvSHQn9zMr-zQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265535"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265535/GD2_or_HER2_targeting_T_cell_engaging_bispecific_antibodies_to_treat_osteosarcoma"><img alt="Research paper thumbnail of GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma" class="work-thumbnail" src="https://attachments.academia-assets.com/95319682/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265535/GD2_or_HER2_targeting_T_cell_engaging_bispecific_antibodies_to_treat_osteosarcoma">GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma</a></div><div class="wp-workCard_item"><span>Journal of Hematology &amp; Oncology</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background The cure rate for metastatic osteosarcoma has not substantially improved over the past...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background The cure rate for metastatic osteosarcoma has not substantially improved over the past decades. Clinical trials of anti-HER2 trastuzumab or anti-GD2 dinutuximab for metastatic or refractory osteosarcoma were not successful, and neither was immune checkpoint inhibitors (ICIs). Methods We tested various target antigen expressions on osteosarcoma cell lines using flow cytometry and analyzed in vitro T cell engaging BsAb (T-BsAb)-dependent T cell-mediated cytotoxicity using 4-h 51Cr release assay. We tested in vivo anti-tumor activities of T-BsAb targeting GD2 or HER2 in established osteosarcoma cell line or patient-derived xenograft (PDX) mouse models carried out in BALB-Rag2−/−IL-2R-γc-KO (BRG) mice. We also generated ex vivo BsAb-armed T cells (EATs) and studied their tumor-suppressive effect against osteosarcoma xenografts. In order to improve the anti-tumor response, ICIs, anti-human PD-1 (pembrolizumab) or anti-human PD-L1 (atezolizumab) antibodies were tested their syn...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dec8886a7c3d39eee37f1039257b33f8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319682,"asset_id":92265535,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319682/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265535"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265535"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265535; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265534"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265534/A_novel_multimeric_IL15_IL15R%CE%B1_Fc_complex_to_enhance_cancer_immunotherapy"><img alt="Research paper thumbnail of A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy" class="work-thumbnail" src="https://attachments.academia-assets.com/95319676/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265534/A_novel_multimeric_IL15_IL15R%CE%B1_Fc_complex_to_enhance_cancer_immunotherapy">A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy</a></div><div class="wp-workCard_item"><span>OncoImmunology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The role of T cells in controlling human cancers is well known. Their success requires continued ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The role of T cells in controlling human cancers is well known. Their success requires continued persistence in vivo and efficient trafficking to tumor sites, requirements shared by other effectors such as Natural Killer (NK) cells. To date, cytokine IL2 remains the only clinically approved cytokine therapy available to expand, maintain, and activate these effector lymphoid cells, but toxicities can be severe. Cytokine IL15 offers similar T cell proliferation and activation properties, but without the unwanted sideeffects seen with IL2. Several IL15-cytokine fusion proteins have been developed to improve their in vivo function, typically exploiting the IL15Rα to complex with IL15, to extend serum half-life and increase affinity for IL15β receptor on immune cells. Here we describe a novel IL15 complex incorporating the fulllength IL15Rα to complex with wild type IL15 to form spontaneous trimers of dimers (6 IL15 + 6 IL15Rα) during co-expression, resulting in a substantial increase in serum half-life and enhancement of in vivo cytokine effect on IgG or T cell engaging antibody-dependent cell-mediated cytotoxicities, when compared to alternative strategies.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e350185e1b70f7d312857715398892b3" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319676,"asset_id":92265534,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319676/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265534"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265534"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265534; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265534]").text(description); $(".js-view-count[data-work-id=92265534]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265534; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265534']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265533"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265533/Overcoming_Tumor_Heterogeneity_by_Ex_Vivo_Arming_of_T_Cells_Using_Multiple_Bispecific_Antibodies"><img alt="Research paper thumbnail of Overcoming Tumor Heterogeneity by Ex Vivo Arming of T Cells Using Multiple Bispecific Antibodies" class="work-thumbnail" src="https://attachments.academia-assets.com/95319769/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265533/Overcoming_Tumor_Heterogeneity_by_Ex_Vivo_Arming_of_T_Cells_Using_Multiple_Bispecific_Antibodies">Overcoming Tumor Heterogeneity by Ex Vivo Arming of T Cells Using Multiple Bispecific Antibodies</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Purpose: Tumoral heterogeneity is a hallmark of tumor evolution and cancer progression, being a l...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Purpose: Tumoral heterogeneity is a hallmark of tumor evolution and cancer progression, being a longstanding challenge to targeted immunotherapy. Ex vivo armed T cells (EATs) using IgG-[L]-scFv bispecific antibodies (BsAbs) are potent tumor-specific cytotoxic effectors. To improve the anti-tumor efficacy of EATs against heterogeneous solid tumors, we explored multi-antigen targeting approaches. Methods: Ex vivo expanded T cells were armed with BsAbs built on the IgG-[L]-scFv platform, where an anti-CD3 (huOKT3) scFv was attached to the carboxyl end of both light chains of a tumor specific IgG. Multispecificity was created by combining monospecific EATs, combining BsAbs on the same T cell, or combining specificities on the same antibody. Three multi-antigens targeting EAT strategies were tested: (1) pooled EATs (simultaneous combination of monospecific EATs or alternate EATs (alternating combination of monospecific EATs), (2) dual-EATs or multi-EATs (T cells simultaneously armed with...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c97cc4185f90e0684ae1e47031c6e08f" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319769,"asset_id":92265533,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319769/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265533"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265533"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265533; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c97cc4185f90e0684ae1e47031c6e08f" } } $('.js-work-strip[data-work-id=92265533]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265533,"title":"Overcoming Tumor Heterogeneity by Ex Vivo Arming of T Cells Using Multiple Bispecific Antibodies","internal_url":"https://www.academia.edu/92265533/Overcoming_Tumor_Heterogeneity_by_Ex_Vivo_Arming_of_T_Cells_Using_Multiple_Bispecific_Antibodies","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319769,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319769/thumbnails/1.jpg","file_name":"2021.08.31.458394.full.pdf","download_url":"https://www.academia.edu/attachments/95319769/download_file","bulk_download_file_name":"Overcoming_Tumor_Heterogeneity_by_Ex_Viv.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319769/2021.08.31.458394.full-libre.pdf?1670302883=\u0026response-content-disposition=attachment%3B+filename%3DOvercoming_Tumor_Heterogeneity_by_Ex_Viv.pdf\u0026Expires=1740537266\u0026Signature=FxLXS3U81qnploO4QCZpmG4-IbxZQ-NxPWvRKHhmUvKgEx2pf7yWkjsRVCFikBTCW-sUaviSy3Xhe2Qbag5qkSO-tEeN1Ao~y9dMi6mICR-vNiK9wLFSa5~yhho0roh~D~NH2lMH4loCZdtvRf5wgFaVPDjX7hkPlRj~2FzIOCEpCbqQ-9FRmtf8PsUTDoaTKUK9jYg3W-TC1O5D2BGmOa9mmG1xyuycFnCxnAh9gC4yxszBzdXtgYPrYFhhD3DI2LZsqmrjsG-3gTvtvuxGuUi-oKQv~AbBusDHuqpYs29ZkBGQ6gK2lipQtWW~s4vJD~kV8ZgGJTC6vksKTTDH8Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="16577953" id="papers"><div class="js-work-strip profile--work_container" data-work-id="127783960"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/127783960/Desensitizing_the_autonomic_nervous_system_to_mitigate_anti_GD2_monoclonal_antibody_side_effects"><img alt="Research paper thumbnail of Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects" class="work-thumbnail" src="https://attachments.academia-assets.com/121466781/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/127783960/Desensitizing_the_autonomic_nervous_system_to_mitigate_anti_GD2_monoclonal_antibody_side_effects">Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects</a></div><div class="wp-workCard_item"><span>Frontiers in oncology</span><span>, May 15, 2024</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of p...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs. Methods: Through confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested. Results: Through confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational superresolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f03d7c1b069f22f24d9dc3904cd0d531" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":121466781,"asset_id":127783960,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/121466781/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="127783960"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="127783960"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 127783960; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="121197500"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/121197500/Bispecific_antibody_does_not_induce_T_cell_death_mediated_by_chimeric_antigen_receptor_against_disialoganglioside_GD2"><img alt="Research paper thumbnail of Bispecific antibody does not induce T-cell death mediated by chimeric antigen receptor against disialoganglioside GD2" class="work-thumbnail" src="https://attachments.academia-assets.com/116141120/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/121197500/Bispecific_antibody_does_not_induce_T_cell_death_mediated_by_chimeric_antigen_receptor_against_disialoganglioside_GD2">Bispecific antibody does not induce T-cell death mediated by chimeric antigen receptor against disialoganglioside GD2</a></div><div class="wp-workCard_item"><span>OncoImmunology</span><span>, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy approaches for retargeting lymphocytes toward cancer cells. Despite their success in lymphoblastic leukemia, solid tumors have been more recalcitrant. Identifying therapeutic barriers facing CARmodified (CART) or BsAb-redirected T (BsAb-T) cells should facilitate their clinical translation to solid tumors. Novel lentiviral vectors containing low-affinity or high-affinity 4-1BB second-generation anti-GD2 (disialoganglioside) CARs were built to achieve efficient T cell transduction. The humanized anti-GD2 £ CD3 BsAb using the IgG-scFv platform was described previously. CART and BsAbengaged T cells were tested for viability, proliferation, and activation/exhaustion marker expression, and in vitro cytotoxicity against GD2(C) tumor cells. The antitumor effect of CAR-grafted and BsAb-T cells was compared in a human melanoma xenograft model. The majority of high CAR density T cells were depleted upon exposure to GD2(C) target cells while the BsAb-T cells survived. The in vitro cytotoxicity of the surviving CART cells was inferior to that of the BsAb-T cells. Using lowaffinity CARs, inclusion of the 4-1BB co-stimulatory domain or exclusion of a co-stimulatory domain, or blocking PD1 did not prevent CART cell depletion. Both CART cells and BsAb-T cells penetrated established subcutaneous human melanoma xenografts; while both induced tumor regression, BsAb was more efficient. The fate of T cells activated by BsAb differs substantially from that by CAR, translating into a more robust antitumor effect both in vitro and in vivo.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="10918f5cb33cf880f3e3e5db6ba8aa25" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":116141120,"asset_id":121197500,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/116141120/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="121197500"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="121197500"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 121197500; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="117044641"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/117044641/Assessing_telomeric_DNA_content_in_pediatric_cancers_using_whole_genome_sequencing_data"><img alt="Research paper thumbnail of Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data" class="work-thumbnail" src="https://attachments.academia-assets.com/113008764/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/117044641/Assessing_telomeric_DNA_content_in_pediatric_cancers_using_whole_genome_sequencing_data">Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data</a></div><div class="wp-workCard_item"><span>Genome Biology</span><span>, 2012</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background: Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background: Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers. Results: To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations. Conclusions: Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="81434565fdc024a7dd9f34458110e6c5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113008764,"asset_id":117044641,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113008764/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="117044641"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="117044641"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 117044641; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "81434565fdc024a7dd9f34458110e6c5" } } $('.js-work-strip[data-work-id=117044641]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":117044641,"title":"Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data","internal_url":"https://www.academia.edu/117044641/Assessing_telomeric_DNA_content_in_pediatric_cancers_using_whole_genome_sequencing_data","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":113008764,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/113008764/thumbnails/1.jpg","file_name":"pmc3580411.pdf","download_url":"https://www.academia.edu/attachments/113008764/download_file","bulk_download_file_name":"Assessing_telomeric_DNA_content_in_pedia.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/113008764/pmc3580411-libre.pdf?1712198864=\u0026response-content-disposition=attachment%3B+filename%3DAssessing_telomeric_DNA_content_in_pedia.pdf\u0026Expires=1740537266\u0026Signature=Wugr8mkZW7wvQr-S2AxwYcZyBSLrNyjdK06p2a51HdBTniL9zmds9UxkSTChyi7zfhu6judGqHO9Rvy6u4KlSoXfK7rGk290~YOCjp2Pp3BWXULqx6jZnDBydVY-znWTE692MOOzLJE-4jFV87IhWIWWEdHAiDQHObVC8hs7l1HnhvpXzRNrEdUqvfn8nBozJ9-xgGp7migjSWB-5omeOOnm8Bqp1c0oUyzMIaGrHYF5FA2rDM1XVlu4uTbUcH6lvPmfi92sa0iN4xsJhky0zsCGz~ohEOiWcIz-rKsZ7fCwPn81gWnq8DKn-i9GPSzW771t6Shc8B5yW6BY4Wvp-Q__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="102746915"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/102746915/GD2_targeted_immunotherapy_and_radioimmunotherapy"><img alt="Research paper thumbnail of GD2-targeted immunotherapy and radioimmunotherapy" class="work-thumbnail" src="https://attachments.academia-assets.com/102934372/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/102746915/GD2_targeted_immunotherapy_and_radioimmunotherapy">GD2-targeted immunotherapy and radioimmunotherapy</a></div><div class="wp-workCard_item"><span>Seminars in oncology</span><span>, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Ganglioside GD2 is a tumor-associated surface antigen found in a broad spectrum of human cancers ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Ganglioside GD2 is a tumor-associated surface antigen found in a broad spectrum of human cancers and stem cells. They include pediatric embryonal tumors (neuroblastoma, retinoblastoma, brain tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma), as well as adult cancers (small cell lung cancer, melanoma, soft tissue sarcomas). Because of its restricted normal tissue distribution, GD2 has been proven safe for antibody targeting. Anti-GD2 antibody is now incorporated into the standard of care for the treatment of high-risk metastatic neuroblastoma. Building on this experience, novel combinations of antibodies, cytokines, cells, and genetically engineered products all directed at GD2 are rapidly moving into the clinic. In this review, past and present immunotherapy trials directed at GD2 will be summarized, highlighting the lessons learned and the future directions.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="634dcc42ad50c0ac8d89032c0096e53d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":102934372,"asset_id":102746915,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/102934372/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="102746915"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="102746915"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 102746915; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265549"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265549/Phase_I_Trial_of_Oral_Yeast_Derived_%CE%B2_Glucan_to_Enhance_Anti_GD2_Immunotherapy_of_Resistant_High_Risk_Neuroblastoma"><img alt="Research paper thumbnail of Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma" class="work-thumbnail" src="https://attachments.academia-assets.com/95319686/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265549/Phase_I_Trial_of_Oral_Yeast_Derived_%CE%B2_Glucan_to_Enhance_Anti_GD2_Immunotherapy_of_Resistant_High_Risk_Neuroblastoma">Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma</a></div><div class="wp-workCard_item"><span>Cancers</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance ant...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of complement-activating monoclonal antibodies. We conducted a phase I study (clinicaltrials.gov NCT00492167) to determine the safety of the combination of yeast-derived beta glucan (BG) and anti-GD2 murine monoclonal antibody 3F8 in patients with relapsed or refractory high-risk neuroblastoma. Patients received intravenous 3F8 (fixed dose of 10 mg/m2/day × 10 days) and oral BG (dose-escalated from 10–200 mg/kg/day × 17 days in cohorts of 3–6 patients each). Forty-four patients completed 141 cycles. One patient developed DLT: transient self-limiting hepatic transaminase elevation 5 days after starting BG (120 mg/kg/day). Overall, 1, 3, 12 and 24 evaluable patients had complete response, partial response, stable and progressive disease, respectively, at the end of treatment. Positive human anti-mouse antibody response and dectin-1 rs3901533 polymorphism were associate...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="be92aa188dcbbfedd2b1a8cf129a67ed" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319686,"asset_id":92265549,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319686/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265549"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265549"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265549; 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</script> <div class="js-work-strip profile--work_container" data-work-id="92265546"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265546/Influence_of_Fc_Modifications_and_IgG_Subclass_on_Biodistribution_of_Humanized_Antibodies_Targeting_L1CAM"><img alt="Research paper thumbnail of Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM" class="work-thumbnail" src="https://attachments.academia-assets.com/95319771/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265546/Influence_of_Fc_Modifications_and_IgG_Subclass_on_Biodistribution_of_Humanized_Antibodies_Targeting_L1CAM">Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM</a></div><div class="wp-workCard_item"><span>Journal of Nuclear Medicine</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Immuno-PET is a powerful tool to noninvasively characterize the in vivo biodistribution of engine...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Immuno-PET is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies. Methods: L1 cell adhesion molecule-targeting humanized (HuE71) IgG 1 and IgG 4 antibodies bearing identical variable heavy-and light-chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with 89 Zr, and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results: In addition to showing uptake in L1 cell adhesion molecule-expressing SKOV3 tumors, as does its parental counterpart HuE71 IgG 1 , the afucosylated variant having enhanced Fc-receptor affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG 1 with abrogated Fc-receptor binding did not show lymphoid uptake. The use of the IgG 4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline in the hinge region of the IgG 4 antibody to mitigate in vivo fragment antigen-binding arm exchange. Conclusion: Our findings highlight the influence of Fc modifications and the choice of IgG subclass on the in vivo biodistribution of antibodies and the potential outcomes thereof.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="f388eeb727f08ebbccf84a2b38887fe1" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319771,"asset_id":92265546,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319771/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265546"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265546"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265546; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265546]").text(description); $(".js-view-count[data-work-id=92265546]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265546; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265546']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "f388eeb727f08ebbccf84a2b38887fe1" } } $('.js-work-strip[data-work-id=92265546]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265546,"title":"Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM","internal_url":"https://www.academia.edu/92265546/Influence_of_Fc_Modifications_and_IgG_Subclass_on_Biodistribution_of_Humanized_Antibodies_Targeting_L1CAM","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319771,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319771/thumbnails/1.jpg","file_name":"629.full.pdf","download_url":"https://www.academia.edu/attachments/95319771/download_file","bulk_download_file_name":"Influence_of_Fc_Modifications_and_IgG_Su.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319771/629.full-libre.pdf?1670302838=\u0026response-content-disposition=attachment%3B+filename%3DInfluence_of_Fc_Modifications_and_IgG_Su.pdf\u0026Expires=1740537266\u0026Signature=CFTEyLbPAiJCwa~VoCp7k-zqr5S2Z4evkj9vD5vPsRJCN7F8p8qYsQXiDxUhVlVHykPMqMAcfe1yfPEzCB9DGMWJ8sKjdqLgzSoXKdk7TQAdmkVMHWX3SFDnbAD2Nj9E5JDjOyPuqMXcsPqvDj1CStiRXd5WyPc2Xb~RO~wvjfVEtLf3xjQMWDcJkZQ1jURtb~5WPjyROQ8dQXRQT~YakcJ2hNkX8XbAZwXoeXzuPJQs9YhSTpJ~uCYDs6K~uKzp-M8eSNBEtwGgkUFefqGO-vhORHb6hnCBWQMCsuwpMAH4Vtf5o3vp~TfzFoA9Iyd23svmT1uT0nfIgcMH2po6Zg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265545"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265545/Posterior_reversible_encephalopathy_syndrome_in_neuroblastoma_patients_receiving_anti_GD23F8_monoclonal_antibody"><img alt="Research paper thumbnail of Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD23F8 monoclonal antibody" class="work-thumbnail" src="https://attachments.academia-assets.com/95319681/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265545/Posterior_reversible_encephalopathy_syndrome_in_neuroblastoma_patients_receiving_anti_GD23F8_monoclonal_antibody">Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD23F8 monoclonal antibody</a></div><div class="wp-workCard_item"><span>Cancer</span><span>, Apr 30, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background-Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background-Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic findings with rapid onset and potentially dire consequences. Patients experience hypertension, seizures, headache, visual disturbance, and/or altered mentation. Magnetic resonance imaging shows edematous changes in brain (especially parietal and occipital lobes). We report PRES associated with anti-G D2 monoclonal antibody (MoAb) immunotherapy which is now standard for high-risk neuroblastoma but has not previously been implicated in PRES. Methods-Successive clinical trials using the anti-G D2 MoAb 3F8 for neuroblastoma patients involved multiple cycles of standard-dose 3F8 (SD-3F8) (20 mg/m 2 /day, x5 days/cycle) or two cycles of high-dose 3F8 (HD-3F8) (80 mg/m 2 /day, x5 days/cycle) followed by cycles of SD-3F8. Results-PRES was diagnosed in 5/215 (2.3%) patients, including 3/160 (1.9%) patients receiving SD-3F8 and 2/55 (3.6%) patients receiving HD-3F8 (p=0.6). All five patients had a rapid return to clinical-radiologic baseline. PRES occurred in 3/26 (11.5%) patients whose prior</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="7dae1d155c098a5f79a8a00ae0584169" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319681,"asset_id":92265545,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319681/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265545"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265545"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265545; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265544"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/92265544/T_Cell_Mediated_Suppression_to_the_Terpolymer_poly_Glu_Lys_Phe_n_"><img alt="Research paper thumbnail of T-Cell-Mediated Suppression to the Terpolymer poly-(Glu, Lys, Phe)n*" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/92265544/T_Cell_Mediated_Suppression_to_the_Terpolymer_poly_Glu_Lys_Phe_n_">T-Cell-Mediated Suppression to the Terpolymer poly-(Glu, Lys, Phe)n*</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Intravenous injection of hapten-conjugated syngeneic cells results in specific immunological tole...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Intravenous injection of hapten-conjugated syngeneic cells results in specific immunological tolerance affecting both hapten-specific contact sensitivity and plaqueforming cell responses (1-4). Although the underlying basis for this nonresponsiveness is not fully understood, it appears that both the T- and B-cell compartments may be affected (3-5). In addition, several studies have reported the generation of specific suppressor T cells under these conditions (4-6). The antigen that was used to induce specific nonresponsiveness (suppression) in these studies was the synthetic linear polypeptide of L-glutamic acid, L-lysine and L-phenylalanine (GLO). 1 This antigen was chosen for several reasons. (a) The immune response to GL4 is under histocompatibility-linked immune response gene control (7). (b) Although previous attempts to identify GLO specific suppressor T cells in nonresponder mice have been unsuccessful (8, 9), we questioned whether induction with antigen-modified syngeneic ce...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265544"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265544"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265544; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265540"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/92265540/Procedes_pour_la_detection_de_maladie_residuelle_minimale"><img alt="Research paper thumbnail of Procedes pour la detection de maladie residuelle minimale" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/92265540/Procedes_pour_la_detection_de_maladie_residuelle_minimale">Procedes pour la detection de maladie residuelle minimale</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">La presente invention a trait a des procedes et des compositions pour l&#39;identification de mar...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">La presente invention a trait a des procedes et des compositions pour l&#39;identification de marqueurs de maladie residuelle minimale, ainsi qu&#39;a des marqueurs de cellules metastatiques. La presente invention a egalement trait a des procedes pour la detection de maladie residuelle minimale et de cellule metastatique chez un sujet.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265540"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265540"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265540; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265540]").text(description); $(".js-view-count[data-work-id=92265540]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265540; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265540']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=92265540]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265540,"title":"Procedes pour la detection de maladie residuelle minimale","internal_url":"https://www.academia.edu/92265540/Procedes_pour_la_detection_de_maladie_residuelle_minimale","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265539"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265539/Immunotherapy_and_Radioimmunotherapy_for_Desmoplastic_Small_Round_Cell_Tumor"><img alt="Research paper thumbnail of Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor" class="work-thumbnail" src="https://attachments.academia-assets.com/95319774/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265539/Immunotherapy_and_Radioimmunotherapy_for_Desmoplastic_Small_Round_Cell_Tumor">Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor</a></div><div class="wp-workCard_item"><span>Frontiers in Oncology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primari...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primarily affects adolescent and young adult males. The 5-year survival rate is 15-30% and few curative treatment options exist. Although there is no standard treatment for DSRCT, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of PDGFA and IGF-1R, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. As in cancer in general, interest in immunotherapy to treat DSRCT has increased in recent years. To that end, several types of immunotherapy are now being tested clinically, including monoclonal antibodies, radionuclide-conjugated antibodies, chimeric antigen receptor T cells, checkpoint inhibitors, and bispecific antibodies (BsAbs). These types of therapies may be particularly useful in DSRCT, which is frequently characterized by widespread intraperitoneal implants, which are di...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="df055a20f72bfe9a9bb8ffa029b87cdb" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319774,"asset_id":92265539,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319774/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265539"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265539"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265539; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265539]").text(description); $(".js-view-count[data-work-id=92265539]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265539; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265539']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "df055a20f72bfe9a9bb8ffa029b87cdb" } } $('.js-work-strip[data-work-id=92265539]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265539,"title":"Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor","internal_url":"https://www.academia.edu/92265539/Immunotherapy_and_Radioimmunotherapy_for_Desmoplastic_Small_Round_Cell_Tumor","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319774,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319774/thumbnails/1.jpg","file_name":"pdf.pdf","download_url":"https://www.academia.edu/attachments/95319774/download_file","bulk_download_file_name":"Immunotherapy_and_Radioimmunotherapy_for.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319774/pdf-libre.pdf?1670302836=\u0026response-content-disposition=attachment%3B+filename%3DImmunotherapy_and_Radioimmunotherapy_for.pdf\u0026Expires=1740537266\u0026Signature=W1cFhYxip2WS8zHN3WYLDqIlAmNfcXTr9chqYIQmp83Vq3cOLWBdKDpA5rKwEVM~y3prCqWBP~G4cJS8iZMdeb3kyo~Edvmp7P5WKzKW4QaJorpvSXahEdsAcKhfCe0Uz7vGx-0yGyqow-uALIkocMUU~wdwHzCWn1gEDmIV3p8Sfym80dD7ZLRdKBj~ZPIfgs7YSD2FIdsBw4Z7OBI3bo1rk-rgxe1Kjhs2zok2ApYoSxTHigavCOMkv7NBwqykizu2MWGSTvYvrKZ0s7Ne89LXK5Xrwz0l9ToJVhTX286IVPzOhKSbPnec8NMg1xNenD0Mj19fFBvvrFT3azpXeQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265538"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265538/Modulating_tumor_infiltrating_myeloid_cells_to_enhance_bispecific_antibody_driven_T_cell_infiltration_and_anti_tumor_response"><img alt="Research paper thumbnail of Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response" class="work-thumbnail" src="https://attachments.academia-assets.com/95319680/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265538/Modulating_tumor_infiltrating_myeloid_cells_to_enhance_bispecific_antibody_driven_T_cell_infiltration_and_anti_tumor_response">Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response</a></div><div class="wp-workCard_item"><span>Journal of Hematology &amp; Oncology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background Tumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesi...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background Tumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesis, growth, proliferation, and metastasis, while derailing the host anti-tumor response. TME impedes bispecific antibody (BsAb) or chimeric antigen receptor (CAR)-driven T cells infiltration, survival, and cytotoxic efficacy. Modulating tumor infiltrating myeloid cells (TIMs) could potentially improve the efficacy of BsAb. Methods We evaluated the effects of TIM modulation on BsAb-driven T cell infiltration into tumors, their persistence, and in vivo anti-tumor response. Anti-GD2 BsAb and anti-HER2 BsAb built on IgG-[L]-scFv platform were tested against human cancer xenografts in BALB-Rag2−/−IL-2R-γc-KO (BRG) mice. Depleting antibodies specific for polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic MDSC (M-MDSC), and tumor associated macrophage (TAM) were used to study the role of each TIM component. Dexamethasone, an established anti-inflammatory agent, was tested fo...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e5e2581022da58f642d6c34234939fbf" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319680,"asset_id":92265538,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319680/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265538"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265538"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265538; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265538]").text(description); $(".js-view-count[data-work-id=92265538]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265538; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265538']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265537"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/92265537/Expression_Analysis_of_GD2_by_Immunohistochemistry_in_Invasive_Breast_Carcinoma"><img alt="Research paper thumbnail of Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/92265537/Expression_Analysis_of_GD2_by_Immunohistochemistry_in_Invasive_Breast_Carcinoma">Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma</a></div><div class="wp-workCard_item"><span>Applied Immunohistochemistry & Molecular Morphology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The glycosphingolipid disialoganglioside GD2 is a cell surface-associated antigen expressed on tu...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The glycosphingolipid disialoganglioside GD2 is a cell surface-associated antigen expressed on tumors of neuroectodermal origin that serves as a target of immunotherapy in select cancer types. Information about the expression of GD2 in breast cancer is limited. In the present study, we investigate the utility of GD2 as a potential biomarker for targeted treatment. The study cohort consists of 386 breast carcinomas of several histologic types. GD2 expression was assessed in both whole tumor sections and tissue microarrays with anti-GD2 3F8 monoclonal antibody immunohistochemistry and correlated with clinicopathologic features and survival outcomes. A total of 134 (35%) breast carcinomas were positive for GD2, with a median H-score of 100. 3F8 staining displayed granular and predominantly cytoplasmic or perinuclear patterns, which was confined to the neoplastic tissue in nearly all cases. GD2 positivity was significantly associated with tumor histologic type (P=0.0015), low grade (P&lt;0.0001), estrogen receptor positivity (P&lt;0.0001), low stage (P=0.0014), and multifocality (P=0.022). Event-free survival and overall survival of patients with GD2-positive and GD2-negative tumors were not significantly different. Our results support further assessment of GD2 using the 3F8 antibody as a predictive and prognostic biomarker in breast cancer.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265537"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265537"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265537; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265537]").text(description); $(".js-view-count[data-work-id=92265537]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265537; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265537']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=92265537]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265537,"title":"Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma","internal_url":"https://www.academia.edu/92265537/Expression_Analysis_of_GD2_by_Immunohistochemistry_in_Invasive_Breast_Carcinoma","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265536"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265536/Reciprocal_impacts_of_telomerase_activity_and_tumor_cell_differentiation_in_neuroblastoma_tumor_biology"><img alt="Research paper thumbnail of Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology" class="work-thumbnail" src="https://attachments.academia-assets.com/95319766/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265536/Reciprocal_impacts_of_telomerase_activity_and_tumor_cell_differentiation_in_neuroblastoma_tumor_biology">Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Telomere maintenance and tumor cell differentiation have been separately implicated in neuroblast...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Telomere maintenance and tumor cell differentiation have been separately implicated in neuroblastoma malignancy. Their mechanistic connection is unclear. We analyzed neuroblastoma cell lines and morphologic subclones representing the adrenergic (ADRN) and mesenchymal (MES) differentiation states and uncovered sharp differences in their telomere protein and telomerase activity levels. Pharmacologic conversion of ADRN into MES cells elicited consistent and robust changes in the expression of telomere-related proteins. Conversely, stringent down-regulation of telomerase activity triggers the differentiation of ADRN into MES cells, which was reversible upon telomerase upregulation. Interestingly, the MES differentiation state is associated with elevated levels of innate immunity factors, including key components of the DNA-sensing pathway. Accordingly, MES but not ADRN cells can mount a robust response to viral infections in vitro. A gene expression signature based on telomere and cell ...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="29c67e2c421cfbfedcd8b30b08a290f8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319766,"asset_id":92265536,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319766/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265536"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265536"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265536; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=92265536]").text(description); $(".js-view-count[data-work-id=92265536]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 92265536; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='92265536']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "29c67e2c421cfbfedcd8b30b08a290f8" } } $('.js-work-strip[data-work-id=92265536]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":92265536,"title":"Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology","internal_url":"https://www.academia.edu/92265536/Reciprocal_impacts_of_telomerase_activity_and_tumor_cell_differentiation_in_neuroblastoma_tumor_biology","owner_id":248743680,"coauthors_can_edit":true,"owner":{"id":248743680,"first_name":"Nai-Kong","middle_initials":null,"last_name":"Cheung","page_name":"NaiKongCheung","domain_name":"independent","created_at":"2022-12-05T20:47:05.842-08:00","display_name":"Nai-Kong Cheung","url":"https://independent.academia.edu/NaiKongCheung"},"attachments":[{"id":95319766,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/95319766/thumbnails/1.jpg","file_name":"2021.05.09.442765.full.pdf","download_url":"https://www.academia.edu/attachments/95319766/download_file","bulk_download_file_name":"Reciprocal_impacts_of_telomerase_activit.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/95319766/2021.05.09.442765.full-libre.pdf?1670302858=\u0026response-content-disposition=attachment%3B+filename%3DReciprocal_impacts_of_telomerase_activit.pdf\u0026Expires=1740537266\u0026Signature=YwGRhjaeJZ9kM-q76BQtuF8YpfremF84WChU1BxX~xGOsD9iGFRkuNNcATL4CABuhUBXp~zKwb2uxaHpJ8g2-SH8fxtbeEei3vvb7eOgosvDesNiE~Lm2a0xMItZobd2uIeslvQIQU6By55qrfYftS20srumzMjWWJ8RdjgwhAYZmWCAyqHlS~l9gbUokHlSVpD26oQd6ZtLo34dtPZ-Jl3I4rb8X3Xn7Lt1z1ck~xIjXoZkPmANPQsodF6oNwLqdKjiSvRNgghOD3WIhQWUXQEj~5sb3WdFJjzsyICmKaBP6iJrGFNFl3sFGyowUfmEdTsN6~gpolvSHQn9zMr-zQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265535"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265535/GD2_or_HER2_targeting_T_cell_engaging_bispecific_antibodies_to_treat_osteosarcoma"><img alt="Research paper thumbnail of GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma" class="work-thumbnail" src="https://attachments.academia-assets.com/95319682/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265535/GD2_or_HER2_targeting_T_cell_engaging_bispecific_antibodies_to_treat_osteosarcoma">GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma</a></div><div class="wp-workCard_item"><span>Journal of Hematology &amp; Oncology</span><span>, 2020</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Background The cure rate for metastatic osteosarcoma has not substantially improved over the past...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Background The cure rate for metastatic osteosarcoma has not substantially improved over the past decades. Clinical trials of anti-HER2 trastuzumab or anti-GD2 dinutuximab for metastatic or refractory osteosarcoma were not successful, and neither was immune checkpoint inhibitors (ICIs). Methods We tested various target antigen expressions on osteosarcoma cell lines using flow cytometry and analyzed in vitro T cell engaging BsAb (T-BsAb)-dependent T cell-mediated cytotoxicity using 4-h 51Cr release assay. We tested in vivo anti-tumor activities of T-BsAb targeting GD2 or HER2 in established osteosarcoma cell line or patient-derived xenograft (PDX) mouse models carried out in BALB-Rag2−/−IL-2R-γc-KO (BRG) mice. We also generated ex vivo BsAb-armed T cells (EATs) and studied their tumor-suppressive effect against osteosarcoma xenografts. In order to improve the anti-tumor response, ICIs, anti-human PD-1 (pembrolizumab) or anti-human PD-L1 (atezolizumab) antibodies were tested their syn...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dec8886a7c3d39eee37f1039257b33f8" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319682,"asset_id":92265535,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319682/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265535"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265535"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265535; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265534"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265534/A_novel_multimeric_IL15_IL15R%CE%B1_Fc_complex_to_enhance_cancer_immunotherapy"><img alt="Research paper thumbnail of A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy" class="work-thumbnail" src="https://attachments.academia-assets.com/95319676/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265534/A_novel_multimeric_IL15_IL15R%CE%B1_Fc_complex_to_enhance_cancer_immunotherapy">A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy</a></div><div class="wp-workCard_item"><span>OncoImmunology</span><span>, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The role of T cells in controlling human cancers is well known. Their success requires continued ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The role of T cells in controlling human cancers is well known. Their success requires continued persistence in vivo and efficient trafficking to tumor sites, requirements shared by other effectors such as Natural Killer (NK) cells. To date, cytokine IL2 remains the only clinically approved cytokine therapy available to expand, maintain, and activate these effector lymphoid cells, but toxicities can be severe. Cytokine IL15 offers similar T cell proliferation and activation properties, but without the unwanted sideeffects seen with IL2. Several IL15-cytokine fusion proteins have been developed to improve their in vivo function, typically exploiting the IL15Rα to complex with IL15, to extend serum half-life and increase affinity for IL15β receptor on immune cells. Here we describe a novel IL15 complex incorporating the fulllength IL15Rα to complex with wild type IL15 to form spontaneous trimers of dimers (6 IL15 + 6 IL15Rα) during co-expression, resulting in a substantial increase in serum half-life and enhancement of in vivo cytokine effect on IgG or T cell engaging antibody-dependent cell-mediated cytotoxicities, when compared to alternative strategies.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e350185e1b70f7d312857715398892b3" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319676,"asset_id":92265534,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319676/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265534"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265534"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265534; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="92265533"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/92265533/Overcoming_Tumor_Heterogeneity_by_Ex_Vivo_Arming_of_T_Cells_Using_Multiple_Bispecific_Antibodies"><img alt="Research paper thumbnail of Overcoming Tumor Heterogeneity by Ex Vivo Arming of T Cells Using Multiple Bispecific Antibodies" class="work-thumbnail" src="https://attachments.academia-assets.com/95319769/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/92265533/Overcoming_Tumor_Heterogeneity_by_Ex_Vivo_Arming_of_T_Cells_Using_Multiple_Bispecific_Antibodies">Overcoming Tumor Heterogeneity by Ex Vivo Arming of T Cells Using Multiple Bispecific Antibodies</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Purpose: Tumoral heterogeneity is a hallmark of tumor evolution and cancer progression, being a l...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Purpose: Tumoral heterogeneity is a hallmark of tumor evolution and cancer progression, being a longstanding challenge to targeted immunotherapy. Ex vivo armed T cells (EATs) using IgG-[L]-scFv bispecific antibodies (BsAbs) are potent tumor-specific cytotoxic effectors. To improve the anti-tumor efficacy of EATs against heterogeneous solid tumors, we explored multi-antigen targeting approaches. Methods: Ex vivo expanded T cells were armed with BsAbs built on the IgG-[L]-scFv platform, where an anti-CD3 (huOKT3) scFv was attached to the carboxyl end of both light chains of a tumor specific IgG. Multispecificity was created by combining monospecific EATs, combining BsAbs on the same T cell, or combining specificities on the same antibody. Three multi-antigens targeting EAT strategies were tested: (1) pooled EATs (simultaneous combination of monospecific EATs or alternate EATs (alternating combination of monospecific EATs), (2) dual-EATs or multi-EATs (T cells simultaneously armed with...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c97cc4185f90e0684ae1e47031c6e08f" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":95319769,"asset_id":92265533,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/95319769/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="92265533"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="92265533"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 92265533; 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