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(PDF) New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells
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The 3 MAbs, 7A4, 2A6 and IG8, detected an" /> <title>(PDF) New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells</title> <link rel="canonical" href="https://www.academia.edu/25329049/New_anti_GD2_monoclonal_antibodies_produced_from_gamma_interferon_treated_neuroblastoma_cells" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 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window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":25329049,"created_at":"2016-05-14T13:13:37.622-07:00","from_world_paper_id":153152059,"updated_at":"2024-11-18T06:36:57.213-08:00","_data":{"grobid_abstract":"Three monoclonal antibodies (IgG,) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gammainterferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectodermderived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 'Wlabelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.","publication_date":"1989,,","publication_name":"International Journal of Cancer","grobid_abstract_attachment_id":"45678262"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [48721591]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Three monoclonal antibodies (IgG,) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gammainterferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectodermderived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 'Wlabelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":45678262,"attachmentType":"pdf","workUrl":"https://www.academia.edu/25329049/New_anti_GD2_monoclonal_antibodies_produced_from_gamma_interferon_treated_neuroblastoma_cells"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":45678262,"attachmentType":"pdf","workUrl":"https://www.academia.edu/25329049/New_anti_GD2_monoclonal_antibodies_produced_from_gamma_interferon_treated_neuroblastoma_cells"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas" data-impression-entity-id="25329049" data-impression-entity-type="2" data-impression-source="signup-banner"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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This chimeric antibody proved to be more effective than 14.G2a in mediating the lysis of neuroblastoma cells with human effector cells, such as granulocytes and natural killer cells within the peripheral blood mononuclear cell population. A comparison of these two effector cell populations isolated from the same donor revealed granulocytes to be more effective than peripheral blood mononuclear cells in lysing neuroblastoma cells, which were coated with monoclonal antibody ch14.18. Addition of recombinant human granulocyte-macrophage colony-stimulatory factor increased ch14.18-mediated lysis of neuroblastoma cells by granulocytes but not by peripheral blood mononuclear cells. In fact, granulocytes were effective in mediating lysis of neuroblastoma cells coated with ch14.18 irrespective of whether they were obtained from normal...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells","attachmentId":71976096,"attachmentType":"pdf","work_url":"https://www.academia.edu/56738933/Effect_of_a_chimeric_anti_ganglioside_GD2_antibody_on_cell_mediated_lysis_of_human_neuroblastoma_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/56738933/Effect_of_a_chimeric_anti_ganglioside_GD2_antibody_on_cell_mediated_lysis_of_human_neuroblastoma_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="17527387" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17527387/Binding_Activities_and_Antitumor_Properties_of_a_New_Mouse_Human_Chimeric_Antibody_Specific_for_GD2_Ganglioside_Antigen">Binding Activities and Antitumor Properties of a New Mouse/Human Chimeric Antibody Specific for GD2 Ganglioside Antigen</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33311181" href="https://univ-nantes.academia.edu/V%C3%A9roniqueS%C3%A9bille">Véronique Sébille</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Clinical Cancer Research, 2007</p><p class="ds-related-work--abstract ds2-5-body-sm">Purpose: We previously generated a mouse monoclonal antibody (mAb) specific for the tumorassociated GD2 ganglioside antigen. Here, we describe the development of a chimeric anti-GD2 mAb for more effective tumor immunotherapy. Experimental Design: We cloned the cDNA encoding the immunoglobulin light and heavy chains of the 60C3 anti-GD2 mAb, and constructed chimeric genes by linking the cDNA fragments of the variable regions of the murine light and heavy chains to cDNA fragments of the human n and g1constant regions, respectively. Results: The resultant chimeric anti-GD2 mAb, c.60C3, showed identical binding affinity and specificity to that of its murine counterpart. Both c.60C3 and 60C3 were rapidly internalized by tumor cells at 37jC. When human serum and human natural killer cells were used as effectors in complement-mediated cytotoxicity and antibody-dependent cell cytotoxicity, respectively, c.60C3 was more effective in killing GD2-expressing tumor cells. However, c.60C3 was ineffective at inducing cell death by apoptosis, although binding of 60C3 induced apoptotic death in vitro. In an in vivo, GD2-expressing, syngeneic tumor model, i.v. injection of c.60C3, but not of 60C3, significantly suppressed tumor growth in mice (P < 0.0005).</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Binding Activities and Antitumor Properties of a New Mouse/Human Chimeric Antibody Specific for GD2 Ganglioside Antigen","attachmentId":39559909,"attachmentType":"pdf","work_url":"https://www.academia.edu/17527387/Binding_Activities_and_Antitumor_Properties_of_a_New_Mouse_Human_Chimeric_Antibody_Specific_for_GD2_Ganglioside_Antigen","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/17527387/Binding_Activities_and_Antitumor_Properties_of_a_New_Mouse_Human_Chimeric_Antibody_Specific_for_GD2_Ganglioside_Antigen"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="18974737" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18974737/Vaccination_with_anti_idiotype_antibody_ganglidiomab_mediates_a_GD2_specific_anti_neuroblastoma_immune_response">Vaccination with anti-idiotype antibody ganglidiomab mediates a GD2-specific anti-neuroblastoma immune response</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="43897112" href="https://independent.academia.edu/HolgerLode">Holger Lode</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39119598" href="https://greifswald.academia.edu/ChristianeHelm">Christiane Helm</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Immunology, Immunotherapy, 2013</p><p class="ds-related-work--abstract ds2-5-body-sm">Purpose Immunotherapy targeting disialoganglioside GD 2 emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here, we report the induction of a GD 2 -specific immune response with ganglidiomab, a new anti-idiotype antibody to anti-GD 2 antibodies of the 14.18 family. Experimental design and results Ganglidiomab was generated following immunization of Balb/c mice with 14G2a, and splenocytes were harvested to generate hybridoma cells. Clones were screened by ELISA for mouse antibody binding to hu14.18. One positive clone was selected to purify and characterize the secreted IgG protein (j, IgG 1 ). This antibody bound to anti-GD 2 antibodies 14G2a, ch14.18/CHO, hu14.18, and to immunocytokines ch14.18-IL2 and hu14.18-IL2 as well as to NK-92 cells expressing scFv(ch14.18)-zeta receptor. Binding of these anti-GD 2 antibodies to the nominal antigen GD 2 as well as GD 2 -specific lysis of neuroblastoma cells by NK-92-scFv(ch14.18)-zeta cells was competitively inhibited by ganglidiomab, proving GD 2 surrogate function and anti-idiotype characteristics. The dissociation constants of ganglidiomab from anti-GD 2 antibodies ranged from 10.8 ± 5.01 to 53.5 ± 1.92 nM as determined by Biacore analyses. The sequences of framework and complementaritydetermining regions of ganglidiomab were identified. Finally, we demonstrated induction of a GD 2 -specific humoral immune response after vaccination of mice with ganglidiomab effective in mediating GD 2 -specific killing of neuroblastoma cells. Conclusion We generated and characterized a novel antiidiotype antibody ganglidiomab and demonstrated activity against neuroblastoma.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Vaccination with anti-idiotype antibody ganglidiomab mediates a GD2-specific anti-neuroblastoma immune response","attachmentId":40361060,"attachmentType":"pdf","work_url":"https://www.academia.edu/18974737/Vaccination_with_anti_idiotype_antibody_ganglidiomab_mediates_a_GD2_specific_anti_neuroblastoma_immune_response","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18974737/Vaccination_with_anti_idiotype_antibody_ganglidiomab_mediates_a_GD2_specific_anti_neuroblastoma_immune_response"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="23119843" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/23119843/A_Monoclonal_Antibody_to_O_Acetyl_GD2_Ganglioside_and_Not_to_GD2_Shows_Potent_Anti_Tumor_Activity_without_Peripheral_Nervous_System_Cross_Reactivity">A Monoclonal Antibody to O-Acetyl-GD2 Ganglioside and Not to GD2 Shows Potent Anti-Tumor Activity without Peripheral Nervous System Cross-Reactivity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="44819251" href="https://independent.academia.edu/JacquesBarbet">Jacques Barbet</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS ONE, 2011</p><p class="ds-related-work--abstract ds2-5-body-sm">Background: Monoclonal antibodies (mAb) against GD2 ganglioside have been shown to be effective for the treatment of neuroblastoma. Beneficial actions are, however, associated with generalized pain due to the binding of anti-GD2 mAbs to peripheral nerve fibers followed by complement activation. Neuroblastoma cells that express GD2 also express its O-acetyl derivative, O-acetyl-GD2 ganglioside (OAcGD2). Hence, we investigated the distribution of OAcGD2 in human tissues using mAb 8B6 to study the cross-reactivity of mAb 8B6 with human tissues.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A Monoclonal Antibody to O-Acetyl-GD2 Ganglioside and Not to GD2 Shows Potent Anti-Tumor Activity without Peripheral Nervous System Cross-Reactivity","attachmentId":43614873,"attachmentType":"pdf","work_url":"https://www.academia.edu/23119843/A_Monoclonal_Antibody_to_O_Acetyl_GD2_Ganglioside_and_Not_to_GD2_Shows_Potent_Anti_Tumor_Activity_without_Peripheral_Nervous_System_Cross_Reactivity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/23119843/A_Monoclonal_Antibody_to_O_Acetyl_GD2_Ganglioside_and_Not_to_GD2_Shows_Potent_Anti_Tumor_Activity_without_Peripheral_Nervous_System_Cross_Reactivity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="25556019" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/25556019/Structural_characterization_andin_vivo_immunosuppressive_activity_of_neuroblastoma_GD2">Structural characterization andin vivo immunosuppressive activity of neuroblastoma GD2</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32109941" href="https://independent.academia.edu/StephanLadisch">Stephan Ladisch</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Glycoconjugate Journal, 1996</p><p class="ds-related-work--abstract ds2-5-body-sm">Shedding of neuroblastoma gangliosides is positively correlated with tumour progression in patients with neuroblastoma. In assessing the biological activity of these ganglioside molecules, we recently found that total human neuroblastoma gangliosides inhibit cellular immune responses. Here, we have studied the major neuroblastoma gangli.oside, Gin. GD2 was purified by high performance liquid chromatography and structurally characterized by mass spectrometry, hmnunoregulatory effects of GD2 in vivo were then determined in an established murine model. GD2 significantly downregulated the local cellular immune response to an allogeneic cell challenge; the usual increase in mass of the lymph node draining the injection site was reduced by 88%, from 1.52 to 0.19 mg (control versus GD2-treated mice; p < 0.01). In parallel, lymphocyte recovery from each node was also reduced from 2.4 to 1.2 × 106 cells, and lymphocyte DNA synthesis was reduced to half of the control level. These results show that certain shed tumour gangliosides, such as GD2, function as intercellular signalling molecules, downregulate the cellular immune response, and may thereby enhance tumour formation and progression.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Structural characterization andin vivo immunosuppressive activity of neuroblastoma GD2","attachmentId":45888421,"attachmentType":"pdf","work_url":"https://www.academia.edu/25556019/Structural_characterization_andin_vivo_immunosuppressive_activity_of_neuroblastoma_GD2","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/25556019/Structural_characterization_andin_vivo_immunosuppressive_activity_of_neuroblastoma_GD2"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="23119866" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/23119866/Chimeric_antibody_c_8B6_to_O_acetyl_GD2_mediates_the_same_efficient_anti_neuroblastoma_effects_as_therapeutic_ch14_18_antibody_to_GD2_without_antibody_induced_allodynia">Chimeric antibody c.8B6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects as therapeutic ch14.18 antibody to GD2 without antibody induced allodynia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="44819251" href="https://independent.academia.edu/JacquesBarbet">Jacques Barbet</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PloS one, 2014</p><p class="ds-related-work--abstract ds2-5-body-sm">Anti-GD2 antibody is a proven therapy for GD2-positive neuroblastoma. Monoclonal antibodies against GD2, such as chimeric mAb ch14.18, have become benchmarks for neuroblastoma therapies. Pain, however, can limit immunotherapy with anti-GD2 therapeutic antibodies like ch14.18. This adverse effect is attributed to acute inflammation via complement activation on GD2-expressing nerves. Thus, new strategies are needed for the development of treatment intensification strategies to improve the outcome of these patients. We established the mouse-human chimeric antibody c.8B6 specific to OAcGD2 in order to reduce potential immunogenicity in patients and to fill the need for a selective agent that can kill neuroblastoma cells without inducing adverse neurological side effects caused by anti-GD2 antibody immunotherapy. We further analyzed some of its functional properties compared with anti-GD2 ch14.18 therapeutic antibody. With the exception of allodynic activity, we found that antibody c.8B6...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Chimeric antibody c.8B6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects as therapeutic ch14.18 antibody to GD2 without antibody induced allodynia","attachmentId":43614892,"attachmentType":"pdf","work_url":"https://www.academia.edu/23119866/Chimeric_antibody_c_8B6_to_O_acetyl_GD2_mediates_the_same_efficient_anti_neuroblastoma_effects_as_therapeutic_ch14_18_antibody_to_GD2_without_antibody_induced_allodynia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/23119866/Chimeric_antibody_c_8B6_to_O_acetyl_GD2_mediates_the_same_efficient_anti_neuroblastoma_effects_as_therapeutic_ch14_18_antibody_to_GD2_without_antibody_induced_allodynia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="14870723" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14870723/In_vivo_targeting_of_human_neuroblastoma_xenograft_by_anti_GD2_anti_Fc%CE%B3RI_CD64_bispecific_antibody">In vivo targeting of human neuroblastoma xenograft by anti-GD2/anti-FcγRI (CD64) bispecific antibody</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33838499" href="https://curie.academia.edu/SandrineMoutel">Sandrine Moutel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European Journal of Cancer, 1995</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"In vivo targeting of human neuroblastoma xenograft by anti-GD2/anti-FcγRI (CD64) bispecific antibody","attachmentId":43822590,"attachmentType":"pdf","work_url":"https://www.academia.edu/14870723/In_vivo_targeting_of_human_neuroblastoma_xenograft_by_anti_GD2_anti_Fc%CE%B3RI_CD64_bispecific_antibody","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14870723/In_vivo_targeting_of_human_neuroblastoma_xenograft_by_anti_GD2_anti_Fc%CE%B3RI_CD64_bispecific_antibody"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="112298384" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/112298384/Disialoganglioside_GD2_on_human_neuroblastoma_cells_target_antigen_for_monoclonal_antibody_mediated_cytolysis_and_suppression_of_tumor_growth">Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="50179742" href="https://independent.academia.edu/MingYang43">Ming Yang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer research, 1987</p><p class="ds-related-work--abstract ds2-5-body-sm">A murine monoclonal antibody 14.18 specifically recognizes disialoganglioside GD2, the major ganglioside expressed on the surface of human neuroblastoma cells. This monoclonal antibody (Mab) is of immunoglobulin G3 isotype, has an affinity constant (KA) of 3.5 X 10(8) M-1, and reacts preferentially with tumor cells and fresh frozen tumor tissues of neuroectodermal origin in enzyme-linked immunosorbent assay and immunoperoxidase assays, respectively. Mab 14.18 effectively lyses a number of human neuroblastoma cell lines by two distinct mechanisms, i.e., antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. There is a good correlation between the average number of antibody-binding sites per neuroblastoma cell and the amount of cell lysis observed in complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. In addition, Mab 14.18 suppresses establishment as well as growth of progressively growing, established human neuroblastoma tumors in...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth","attachmentId":109570925,"attachmentType":"pdf","work_url":"https://www.academia.edu/112298384/Disialoganglioside_GD2_on_human_neuroblastoma_cells_target_antigen_for_monoclonal_antibody_mediated_cytolysis_and_suppression_of_tumor_growth","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/112298384/Disialoganglioside_GD2_on_human_neuroblastoma_cells_target_antigen_for_monoclonal_antibody_mediated_cytolysis_and_suppression_of_tumor_growth"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="58972060" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/58972060/Neutrophils_are_cytotoxic_and_growth_inhibiting_for_neuroblastoma_cells_with_an_anti_GD2_antibody_but_without_cytotoxicity_can_be_growth_stimulating">Neutrophils are cytotoxic and growth-inhibiting for neuroblastoma cells with an anti-GD2 antibody but, without cytotoxicity, can be growth-stimulating</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37330549" href="https://independent.academia.edu/RonglongChen">Rong-long Chen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Immunology, Immunotherapy, 2000</p><p class="ds-related-work--abstract ds2-5-body-sm">Neutrophils and mononuclear cells (MNC) can mediate antibody-dependent cellular cytotoxicity (ADCC) against cancer cells. To study cytotoxicity and growth inhibition of neuroblastoma cells by neutrophils and MNC with chimeric anti-disialoganglioside (GD2) monoclonal antibody (mAb) ch14.18, we developed digital image microscopy scanning (DIMSCAN) assays that measure¯uorescence of target cells in 96-well plates after 6±18 h (cytotoxicity assay) or 7 days (growth assay). Neuroblastoma cell lines (GD2-positive: SMS-KCN, SMS-LHN, LA-N-1; GD2-negative: SK-N-SH) were preloaded with calcein acetoxymethyl ester for the cytotoxicity assay or labeled in situ after 7 days of culture with¯uorescein diacetate in the growth assay. Fluorescence, as quanti®ed by DIMSCAN, was correlated with neuroblastoma cell number in both assays (100±2000 cells/well). In the cytotoxicity test, both neutrophils and MNC eectively mediated ADCC of GD2positive but not GD2-negative neuroblastoma cell lines. Cytotoxicity of both neutrophils and MNC increased with eector to target cell (E:T) ratio (5±50:1) and mAb ch.14.18 dose (0.1±10 lg/ml). ADCC of neutrophils, but not MNC, increased with addition of GM-CSF. Neutrophils, especially with rhGM-CSF, signi®cantly suppressed growth of GD2-positive cell lines at a high E:T ratio (50:1) and mAb dose (10 lg/ml). Without antibody, neutrophils inhibited growth of one cell line (LA-N-1) but stimulated growth of two others (SMS-KCN, SMS-LHN). If neuroblastoma cells did not express GD2 (SK-N-SH), neutrophils stimulated growth whether or not antibody was present. Neutrophil culture supernatants increased growth of SK-N-SH, LA-N-1, and SMS-KCN cells, and MNC culture supernatants increased growth of SK-N-SH. In conclusion, neutrophils can mediate cytotoxicity and growth inhibition with a chimeric anti-GD2 antibody but also can promote tumor cell growth if antibody is not present or if GD2 is not expressed. Key words ADCC á GD2 á Neutrophils á Digital image microscopy á Calcein-AM á Fluorescein diacetate á Neuroblastoma</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Neutrophils are cytotoxic and growth-inhibiting for neuroblastoma cells with an anti-GD2 antibody but, without cytotoxicity, can be growth-stimulating","attachmentId":73124188,"attachmentType":"pdf","work_url":"https://www.academia.edu/58972060/Neutrophils_are_cytotoxic_and_growth_inhibiting_for_neuroblastoma_cells_with_an_anti_GD2_antibody_but_without_cytotoxicity_can_be_growth_stimulating","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/58972060/Neutrophils_are_cytotoxic_and_growth_inhibiting_for_neuroblastoma_cells_with_an_anti_GD2_antibody_but_without_cytotoxicity_can_be_growth_stimulating"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="122130838" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/122130838/Induction_of_IgG_antibodies_against_the_GD2_carbohydrate_tumor_antigen_by_vaccination_with_peptide_mimotopes">Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by vaccination with peptide mimotopes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41630567" href="https://independent.academia.edu/ArnoldPollak">Arnold Pollak</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European Journal of Immunology, 2006</p><p class="ds-related-work--abstract ds2-5-body-sm">The disialoganglioside GD2, a carbohydrate antigen, is expressed on all tumors of neuroectodermal origin, including melanoma, neuroblastoma, sarcoma and small cell lung cancer. Due to its specific expression on tumor surfaces, GD2 is an attractive target for immunotherapies. The mouse/human chimeric anti‐GD2 mAb ch14.18 is already applied in melanoma and neuroblastoma trials as a passive immunotherapy. To establish an active immunotherapy alternative, we aimed to replace the poorly immunogenic ganglioside with immunogenic peptides. Previously, we used the ch14.18 antibody to select GD2 peptide mimics from a phage display library. In the present study, two mimics of the ch14.18 epitope were coupled to keyhole limpet hemocyanin and used for immunizing BALB/c mice. Induction of a specific humoral immune response towards the original antigen GD2, both purified and expressed on neuroblastoma and melanoma cells, could be demonstrated in ELISA, Western blot, and immunofluorohistochemistry....</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by vaccination with peptide mimotopes","attachmentId":116857054,"attachmentType":"pdf","work_url":"https://www.academia.edu/122130838/Induction_of_IgG_antibodies_against_the_GD2_carbohydrate_tumor_antigen_by_vaccination_with_peptide_mimotopes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/122130838/Induction_of_IgG_antibodies_against_the_GD2_carbohydrate_tumor_antigen_by_vaccination_with_peptide_mimotopes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":45678262,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":45678262,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_45678262" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="25556074" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/25556074/Expression_of_GD2_ganglioside_by_untreated_primary_human_neuroblastomas">Expression of GD2 ganglioside by untreated primary human neuroblastomas</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32109941" href="https://independent.academia.edu/StephanLadisch">Stephan Ladisch</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer research, 1986</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Expression of GD2 ganglioside by untreated primary human neuroblastomas","attachmentId":45888448,"attachmentType":"pdf","work_url":"https://www.academia.edu/25556074/Expression_of_GD2_ganglioside_by_untreated_primary_human_neuroblastomas","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/25556074/Expression_of_GD2_ganglioside_by_untreated_primary_human_neuroblastomas"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="1" data-entity-id="91972845" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/91972845/Generation_and_characterization_of_dimeric_small_immunoproteins_specific_for_neuroblastoma_associated_antigen_GD2">Generation and characterization of dimeric small immunoproteins specific for neuroblastoma associated antigen GD2</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33079365" href="https://independent.academia.edu/OscarBurrone">Oscar Burrone</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Molecular Medicine, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Generation and characterization of dimeric small immunoproteins specific for neuroblastoma associated antigen GD2","attachmentId":95108396,"attachmentType":"pdf","work_url":"https://www.academia.edu/91972845/Generation_and_characterization_of_dimeric_small_immunoproteins_specific_for_neuroblastoma_associated_antigen_GD2","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/91972845/Generation_and_characterization_of_dimeric_small_immunoproteins_specific_for_neuroblastoma_associated_antigen_GD2"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="33824354" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/33824354/Anti_GD2_monoclonal_antibody_immunotherapy_a_promising_strategy_in_the_prevention_of_neuroblastoma_relapse">Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="66111442" href="https://independent.academia.edu/EmilioCosimo">Emilio Cosimo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Letters, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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