{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:05:52Z","timestamp":1789175152605,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Health (NIH)\/National Cancer Institute","award":["1R01CA284065"],"award-info":[{"award-number":["1R01CA284065"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diffuse hemispheric glioma (DHG), H3 G34-mutant, is a highly aggressive and fatal pediatric brain tumor, with a median survival of only \u223c18 months and no effective targeted therapies. While chimeric antigen receptor (CAR) T cell therapy has shown success in B-cell leukemia and promise in other pediatric central nervous system tumors, it has not yet been evaluated explicitly in preclinical or clinical models of DHG. B7-H3 (CD276), a tumor-associated antigen overexpressed in pediatric brain tumors, represents a promising target for immunotherapeutic intervention in DHG. Here, we present the first preclinical evaluation of B7-H3-directed CAR T cell therapy in DHG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated B7-H3 expression in specimens from DHG patients and patient-derived cell lines. Two B7-H3-targeted CAR constructs were generated and evaluated for antigen-specific activation, cytokine production, exhaustion, and cytotoxicity in vitro. Therapeutic efficacy was assessed in multiple orthotopic DHG xenograft models, followed by multiplex immunofluorescence and serum cytokine profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>B7-H3 was highly expressed in DHG tumors and cell lines, but at minimal levels in normal brain tissue. B7-H3 CAR T cells demonstrated potent, antigen-specific cytotoxicity against DHG cells, with negligible activity against B7-H3-knockout DHG cells. In vivo, the intratumoral administration of B7-H3 CAR T cells led to significant tumor regression and a substantial extension of survival in 3 DHG mouse models, with durable tumor eradication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides preclinical evidence supporting B7-H3 CAR T cell therapy as a highly effective immunotherapeutic strategy for DHG. Our findings support B7-H3 as a compelling immunotherapeutic target for DHG, laying the groundwork for clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag185","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:50:33Z","timestamp":1786189833000},"source":"Crossref","is-referenced-by-count":0,"title":["Potent antitumor preclinical efficacy of B7-H3 chimeric antigen receptor (CAR) T cells in H3G34-mutant, diffuse hemispheric glioma"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9733-6069","authenticated-orcid":false,"given":"David","family":"Akhavan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Kansas Cancer Center , Kansas City, Kansas,","place":["USA"]},{"name":"Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center , Kansas City, Kansas, 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