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<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="gMID174lm0DdNCpSFRcckVPM7iJHTIf5korDSOxyczkYd15OcK2wTAvLlBSn9ruqyrsh4nwDphoOw39LowSErQ" /> <meta name="citation_title" content="GD2 CAR T cells against human glioblastoma" /> <meta name="citation_journal_title" content="npj Precision Oncology" /> <meta name="citation_author" content="Marco Bestagno" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/73715840/GD2_CAR_T_cells_against_human_glioblastoma" /> <meta name="twitter:title" content="GD2 CAR T cells against human glioblastoma" /> <meta name="twitter:description" content="Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data" /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/73715840/GD2_CAR_T_cells_against_human_glioblastoma" /> <meta property="og:title" content="GD2 CAR T cells against human glioblastoma" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data" /> <meta property="article:author" content="https://independent.academia.edu/MarcoBestagno" /> <meta name="description" content="Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. 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We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma...","author":[{"@context":"https://schema.org","@type":"Person","name":"Marco Bestagno","url":"https://independent.academia.edu/MarcoBestagno"}],"contributor":[],"dateCreated":"2022-03-14","dateModified":"2024-11-28","headline":"GD2 CAR T cells against human glioblastoma","image":"https://attachments.academia-assets.com/82128533/thumbnails/1.jpg","inLanguage":"en","keywords":[],"publication":"npj Precision Oncology","publisher":{"@context":"https://schema.org","@type":"Organization","name":"Springer Science and Business Media LLC"},"sourceOrganization":[{"@context":"https://schema.org","@type":"EducationalOrganization","name":null}],"thumbnailUrl":"https://attachments.academia-assets.com/82128533/thumbnails/1.jpg","url":"https://www.academia.edu/73715840/GD2_CAR_T_cells_against_human_glioblastoma"}</script><style type="text/css">@media(max-width: 567px){:root{--token-mode: Rebrand;--dropshadow: 0 2px 4px 0 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{"work":{"id":73715840,"created_at":"2022-03-14T00:51:31.568-07:00","from_world_paper_id":198471469,"updated_at":"2024-11-28T12:04:21.607-08:00","_data":{"abstract":"Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma...","publisher":"Springer Science and Business Media LLC","ai_title_tag":"Effective GD2 CAR T Cells Targeting Glioblastoma in Models","publication_name":"npj Precision Oncology"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"GD2 CAR T cells against human glioblastoma","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [32955667]; 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'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":82128533,"attachmentType":"pdf"}"><img alt="First page of “GD2 CAR T cells against human glioblastoma”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/82128533/mini_magick20220314-8231-1cvl0q1.png?1647244378" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">GD2 CAR T cells against human glioblastoma</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="32955667" href="https://independent.academia.edu/MarcoBestagno"><img alt="Profile image of Marco Bestagno" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Marco Bestagno</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">npj Precision Oncology</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">14 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 73715840; 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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">Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma...</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":82128533,"attachmentType":"pdf","workUrl":"https://www.academia.edu/73715840/GD2_CAR_T_cells_against_human_glioblastoma"}">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":82128533,"attachmentType":"pdf","workUrl":"https://www.academia.edu/73715840/GD2_CAR_T_cells_against_human_glioblastoma"}"><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="73715840" 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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Chimeric antigen receptor (CAR)-modified T cells can have potent antitumor activity in B-cell malignancies, and trials to harness this cytolytic activity toward GD2 in neuroblastoma are under way. In an effort to enhance the antitumor activity of CAR T cells that target GD2, we generated variant CAR constructs predicted to improve the stability and the affinity of the GD2-binding, 14G2a-based, single-chain variable fragment (scFv) of the CAR and compared their properties in vivo We included the E101K mutation of GD2 scFv (GD2-E101K) that has enhanced antitumor activity against a GD2+ human neuroblastoma xenograft in vivo However, this enhanced antitumor efficacy in vivo was concomitantly associated with lethal central nervous system (CNS) toxicity comprised of extensive C...</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":"High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model","attachmentId":92129160,"attachmentType":"pdf","work_url":"https://www.academia.edu/88083430/High_Affinity_GD2_Specific_CAR_T_Cells_Induce_Fatal_Encephalitis_in_a_Preclinical_Neuroblastoma_Model","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/88083430/High_Affinity_GD2_Specific_CAR_T_Cells_Induce_Fatal_Encephalitis_in_a_Preclinical_Neuroblastoma_Model"><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="117758981" 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/117758981/Autologous_Patient_Derived_Car_TS_Show_Functional_Deficits_Against_Human_Glioblastoma">Autologous Patient-Derived Car-TS Show Functional Deficits Against Human Glioblastoma</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="303516933" href="https://independent.academia.edu/ZahraAlizada12">Zahra Alizada</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuro-Oncology Advances</p><p class="ds-related-work--abstract ds2-5-body-sm">Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a poor prognosis despite aggressive standard of care. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in liquid malignancies, but clinical trials in GBM targeting various tumor antigens have not shown durable clinical benefit. While this may be attributable to various tumor-intrinsic immune evasion strategies characteristic of GBM, little work has assessed whether the issue is due to the quality of the CAR-T treatment itself. Currently, CAR-Ts for GBMs and liquid malignancies are manufactured in an autologous setting in which T-cells are extracted from patients, engineered ex-vivo, and subsequently reinfused back. However, peripheral T-cells taken from untreated GBM patients have demonstrated qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to establish whether CAR-Ts generated from GBM patients would show reduced efficacy...</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":"Autologous Patient-Derived Car-TS Show Functional Deficits Against Human Glioblastoma","attachmentId":113537326,"attachmentType":"pdf","work_url":"https://www.academia.edu/117758981/Autologous_Patient_Derived_Car_TS_Show_Functional_Deficits_Against_Human_Glioblastoma","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/117758981/Autologous_Patient_Derived_Car_TS_Show_Functional_Deficits_Against_Human_Glioblastoma"><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="45203917" 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/45203917/Targeting_and_killing_glioblastoma_with_monoclonal_antibody_to_i_O_i_acetyl_GD2_ganglioside">Targeting and killing glioblastoma with monoclonal antibody to <i>O</i>-acetyl GD2 ganglioside</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="46873644" href="https://independent.academia.edu/LisaOliver6">Lisa Oliver</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Oncotarget, 2014</p><p class="ds-related-work--abstract ds2-5-body-sm">There are still unmet medical needs in the treatment of glioblastoma, the most common and the most aggressive glioma of all brain tumors. Here, we found that O-acetyl GD2 is expressed in surgically resected human glioblastoma tissue. In addition, we demonstrated that 8B6 monoclonal antibody specific for O-acetylat GD2 could effectively inhibit glioblastoma cell proliferation in vitro and in vivo. Taken together, these results indicate that O-acetylated GD2 represents a novel antigen for immunotherapeutic-based treatment of high-grade gliomas.</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":"Targeting and killing glioblastoma with monoclonal antibody to \u003ci\u003eO\u003c/i\u003e-acetyl GD2 ganglioside","attachmentId":65787318,"attachmentType":"pdf","work_url":"https://www.academia.edu/45203917/Targeting_and_killing_glioblastoma_with_monoclonal_antibody_to_i_O_i_acetyl_GD2_ganglioside","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/45203917/Targeting_and_killing_glioblastoma_with_monoclonal_antibody_to_i_O_i_acetyl_GD2_ganglioside"><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="104064117" 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/104064117/CAR_T_Therapy_for_Pediatric_High_Grade_Gliomas_Peculiarities_Current_Investigations_and_Future_Strategies">CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies</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="190699935" href="https://independent.academia.edu/GiadaDelBaldo">Giada Del Baldo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Immunology</p><p class="ds-related-work--abstract ds2-5-body-sm">High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Immunotherapy is based on different techniques aimed to redirect the patient own immune system to fight specifically cancer cells. In particular, T-lymphocytes can be genetically modified to express chimeric proteins, known as chimeric antigen receptors (CARs), targeting selected tumor-associated antigens (TAA). Disialoganglioside GD2 (GD-2) and B7-H3 are highly expressed on pHGGs and have been evaluated as possible targets in pediatric clinical t...</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":"CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies","attachmentId":103891748,"attachmentType":"pdf","work_url":"https://www.academia.edu/104064117/CAR_T_Therapy_for_Pediatric_High_Grade_Gliomas_Peculiarities_Current_Investigations_and_Future_Strategies","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/104064117/CAR_T_Therapy_for_Pediatric_High_Grade_Gliomas_Peculiarities_Current_Investigations_and_Future_Strategies"><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="108400341" 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/108400341/Optimizing_T_Cell_Based_Therapy_for_Glioblastoma">Optimizing T Cell-Based Therapy for Glioblastoma</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="63772491" href="https://independent.academia.edu/FarhadDastmalchi">Farhad Dastmalchi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Immunology, 2021</p><p class="ds-related-work--abstract ds2-5-body-sm">Evading T cell surveillance is a hallmark of cancer. Patients with solid tissue malignancy, such as glioblastoma (GBM), have multiple forms of immune dysfunction, including defective T cell function. T cell dysfunction is exacerbated by standard treatment strategies such as steroids, chemotherapy, and radiation. Reinvigoration of T cell responses can be achieved by utilizing adoptively transferred T cells, including CAR T cells. However, these cells are at risk for depletion and dysfunction as well. This review will discuss adoptive T cell transfer strategies and methods to avoid T cell dysfunction for the treatment of brain cancer.</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":"Optimizing T Cell-Based Therapy for Glioblastoma","attachmentId":106794692,"attachmentType":"pdf","work_url":"https://www.academia.edu/108400341/Optimizing_T_Cell_Based_Therapy_for_Glioblastoma","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/108400341/Optimizing_T_Cell_Based_Therapy_for_Glioblastoma"><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="93291918" 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/93291918/Glioblastoma_targeted_CD4_CAR_T_cells_mediate_superior_antitumor_activity">Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity</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="250520528" href="https://independent.academia.edu/brendaaguilar234">brenda aguilar</a></div><p class="ds-related-work--metadata ds2-5-body-xs">JCI insight, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic G...</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":"Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity","attachmentId":96069424,"attachmentType":"pdf","work_url":"https://www.academia.edu/93291918/Glioblastoma_targeted_CD4_CAR_T_cells_mediate_superior_antitumor_activity","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/93291918/Glioblastoma_targeted_CD4_CAR_T_cells_mediate_superior_antitumor_activity"><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="114625702" 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/114625702/A_single_dose_of_peripherally_infused_EGFRvIII_directed_CAR_T_cells_mediates_antigen_loss_and_induces_adaptive_resistance_in_patients_with_recurrent_glioblastoma">A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma</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="99940672" href="https://upenn.academia.edu/StevenBrem">Steven Brem</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Science translational medicine, 2017</p><p class="ds-related-work--abstract ds2-5-body-sm">We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up. All patients demonstrated detectable transient expansion of CART-EGFRvIII cells in peripheral blood. Seven patients had post-CART-EGFRvIII surgical intervention, which allowed for tissue-specific analysis of CART-EGFRvIII trafficking to the tumor, phenotyping of tumor-infiltrating T cells and the tumor microenvironment in situ, and analysis of post-therapy EGFRvIII target antigen expression. Imaging findings after CART immunotherapy...</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 single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma","attachmentId":111274269,"attachmentType":"pdf","work_url":"https://www.academia.edu/114625702/A_single_dose_of_peripherally_infused_EGFRvIII_directed_CAR_T_cells_mediates_antigen_loss_and_induces_adaptive_resistance_in_patients_with_recurrent_glioblastoma","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/114625702/A_single_dose_of_peripherally_infused_EGFRvIII_directed_CAR_T_cells_mediates_antigen_loss_and_induces_adaptive_resistance_in_patients_with_recurrent_glioblastoma"><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="87659172" 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/87659172/Proposing_a_tandem_AND_gate_CAR_T_cell_targeting_glioblastoma_multiforme">Proposing a tandem AND-gate CAR T cell targeting glioblastoma multiforme</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="55722614" href="https://independent.academia.edu/SetareSoltani">Setare Soltani</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Medical Hypotheses, 2020</p><p class="ds-related-work--abstract ds2-5-body-sm">CAR T cell therapy is suggested as an effective method to treat hematological malignancies. However, high recurrence rates and in vivo toxicities have limited their widespread use. In order to reduce toxicity and improve tumor specificity, we propose a CAR T cell targeting glioblastoma multiforme utilizing the synNotch receptor pathway linked to a tandem CAR T cell. The extracellular domain of the synNotch receptor is replaced by a single chain fragment variable specific for the EGF receptor variant III (scfv-EGFRvIII), and covalently bonded to a IL-13Rα2-CD133-tandem CAR. This would produce an AND-gate CART cell, which requires activation of both signals from synNotch receptor binding to EGFRvIII and then binding of the tandem CAR to either of the two IL-13Rα2 or CD133 ligands-specific antigens for glioblastoma stem cells. SynNotch receptor activation along with the 4-1BB costimulatory domain results in CAR T cell expression under the TRE promoter, culminating in a trispecific and effective tumor stem cell recognition and elimination of glioblastoma multiforme.</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":"Proposing a tandem AND-gate CAR T cell targeting glioblastoma multiforme","attachmentId":91808898,"attachmentType":"pdf","work_url":"https://www.academia.edu/87659172/Proposing_a_tandem_AND_gate_CAR_T_cell_targeting_glioblastoma_multiforme","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/87659172/Proposing_a_tandem_AND_gate_CAR_T_cell_targeting_glioblastoma_multiforme"><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="11251303" 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/11251303/EGFRvIII_Specific_Chimeric_Antigen_Receptor_T_Cells_Migrate_to_and_Kill_Tumor_Deposits_Infiltrating_the_Brain_Parenchyma_in_an_Invasive_Xenograft_Model_of_Glioblastoma">EGFRvIII-Specific Chimeric Antigen Receptor T Cells Migrate to and Kill Tumor Deposits Infiltrating the Brain Parenchyma in an Invasive Xenograft Model of Glioblastoma</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="27181322" href="https://independent.academia.edu/GabrielDeLeon1">Gabriel De Leon</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">Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumorspecific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII + CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII + CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.</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":"EGFRvIII-Specific Chimeric Antigen Receptor T Cells Migrate to and Kill Tumor Deposits Infiltrating the Brain Parenchyma in an Invasive Xenograft Model of Glioblastoma","attachmentId":46792282,"attachmentType":"pdf","work_url":"https://www.academia.edu/11251303/EGFRvIII_Specific_Chimeric_Antigen_Receptor_T_Cells_Migrate_to_and_Kill_Tumor_Deposits_Infiltrating_the_Brain_Parenchyma_in_an_Invasive_Xenograft_Model_of_Glioblastoma","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/11251303/EGFRvIII_Specific_Chimeric_Antigen_Receptor_T_Cells_Migrate_to_and_Kill_Tumor_Deposits_Infiltrating_the_Brain_Parenchyma_in_an_Invasive_Xenograft_Model_of_Glioblastoma"><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":82128533,"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":82128533,"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_82128533" 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="121585568" 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/121585568/Current_progress_in_chimeric_antigen_receptor_T_cell_therapy_for_glioblastoma_multiforme">Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme</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="284006237" href="https://independent.academia.edu/HanyMarei1">Hany Marei</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Medicine, 2021</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":"Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme","attachmentId":116425433,"attachmentType":"pdf","work_url":"https://www.academia.edu/121585568/Current_progress_in_chimeric_antigen_receptor_T_cell_therapy_for_glioblastoma_multiforme","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/121585568/Current_progress_in_chimeric_antigen_receptor_T_cell_therapy_for_glioblastoma_multiforme"><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="21425400" 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/21425400/Rational_development_and_characterization_of_humanized_anti_EGFR_variant_III_chimeric_antigen_receptor_T_cells_for_glioblastoma">Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma</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="42668289" href="https://independent.academia.edu/GabrielaPlesa">Gabriela Plesa</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42679829" href="https://independent.academia.edu/AlexandriaCogdill">Alexandria Cogdill</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42495160" href="https://independent.academia.edu/JohnScholler">John Scholler</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42530039" href="https://independent.academia.edu/MarcelaMaus">Marcela Maus</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Science Translational Medicine, 2015</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":"Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma","attachmentId":41866587,"attachmentType":"pdf","work_url":"https://www.academia.edu/21425400/Rational_development_and_characterization_of_humanized_anti_EGFR_variant_III_chimeric_antigen_receptor_T_cells_for_glioblastoma","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/21425400/Rational_development_and_characterization_of_humanized_anti_EGFR_variant_III_chimeric_antigen_receptor_T_cells_for_glioblastoma"><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="87799714" 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/87799714/Application_of_blood_brain_barrier_models_in_pre_clinical_assessment_of_glioblastoma_targeting_CAR_T_based_immunotherapies">Application of blood brain barrier models in pre-clinical assessment of glioblastoma- targeting CAR-T based immunotherapies</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="42541481" href="https://independent.academia.edu/ZiyingLiu">Ziying Liu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2022</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":"Application of blood brain barrier models in pre-clinical assessment of glioblastoma- targeting CAR-T based 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Bottino</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="4095218" href="https://hsanmartino.academia.edu/AntonioDaga">Antonio Daga</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Current pharmaceutical design, 2011</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":"New perspectives in glioma immunotherapy","attachmentId":31233367,"attachmentType":"pdf","work_url":"https://www.academia.edu/3489475/New_perspectives_in_glioma_immunotherapy","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" 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2015</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 novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing","attachmentId":40131694,"attachmentType":"pdf","work_url":"https://www.academia.edu/18565575/A_novel_anti_GD2_4_1BB_chimeric_antigen_receptor_triggers_neuroblastoma_cell_killing","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/18565575/A_novel_anti_GD2_4_1BB_chimeric_antigen_receptor_triggers_neuroblastoma_cell_killing"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" 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Clinical oncology, 2018</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":"Current state of immunotherapy for glioblastoma","attachmentId":86320874,"attachmentType":"pdf","work_url":"https://www.academia.edu/79693330/Current_state_of_immunotherapy_for_glioblastoma","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/79693330/Current_state_of_immunotherapy_for_glioblastoma"><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 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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/67471905/Development_of_novel_target_modules_for_retargeting_of_UniCAR_T_cells_to_GD2_positive_tumor_cells">Development of novel target modules for retargeting of UniCAR T cells to GD2 positive tumor cells</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="50251809" href="https://hzdr.academia.edu/JensPietzsch">Jens Pietzsch</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Oncotarget</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":"Development of novel target modules for retargeting of UniCAR T cells to GD2 positive tumor 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