{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:47:49Z","timestamp":1791910069741,"version":"4.3.4"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swim Across America","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/05d8ft347","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ludwig Institute for Cancer Research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/05qdwtz81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Parker Institute for Cancer Immunotherapy","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/0184qbg02","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Terry Fox Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/05vd00053","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Philanthropic Trust","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/04sg26g73","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Glioblastoma (GBM) is a lethal brain tumor with a 95% five-year mortality rate, and remains a major unmet clinical need. An innovative approach to target GBM is administration of chimeric antigen receptor (CAR) T cells. In this study we identified B7-H3 as a favorable target antigen for CAR T cell therapy of GBM and developed a B7-H3 targeting CAR T cell. This CAR demonstrates robust, antigen-specific cytolysis and cytokine production, low tonic signaling, and preservation of a stem\/na\u00efve cell phenotype. Using orthotopic xenograft models of GBM we show that a single intravenous administration of this B7-H3 targeted CAR confers tumor control, and long-term survival. We identified upregulation of T cell inhibitory ligands PD-L1 and PD-L2 as a mechanism of resistance, and modified our B7-H3 targeting CAR vector to include a secreted a PD-1 blocking scFv. We further demonstrate that concomitant PD-1 blockade by the secreted PD-1 blocking scFv augments the antitumor capabilities of B7-H3-targeting CAR T cells through increased intratumoral infiltration by the CAR T cells and improved effector function. These data demonstrate B7-H3 targeting CAR T cells with concomitant PD-1 blockade is a safe and efficient method for improving the antitumor capacity of CAR T cells for GBM.<\/jats:p>","DOI":"10.1172\/jci.insight.196296","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:00:16Z","timestamp":1791907216000},"source":"Crossref","is-referenced-by-count":0,"title":["Locoregionally delivered PD-1 blockade augments B7-H3 targeting CAR T cell efficacy in models of glioblastoma"],"prefix":"10.1172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3444-8108","authenticated-orcid":true,"given":"Jonathan F.","family":"Khan","sequence":"first","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cance, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parwiz","family":"Abrahimi","sequence":"additional","affiliation":[{"name":"Parker Institute 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Immunotherapy and Sandra and Edward Meyer Cance, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Estrada Navarro","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cance, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamadou A.","family":"Bah","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cance, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Hopland","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J.","family":"Purdon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-0515","authenticated-orcid":true,"given":"Ileana C.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Pathology, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Tabar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-2222","authenticated-orcid":true,"given":"Jedd D.","family":"Wolchok","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cance, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Merghoub","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy and Sandra and Edward Meyer Cance, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renier J.","family":"Brentjens","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,13]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/196296\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:00:18Z","timestamp":1791907218000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/196296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.196296"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.196296","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]}}}