biostudies-literatureTheruvath JChildren with Cancer UKNCI NIH HHSNINDS NIH HHSThe Brain Tumour Charity712-719https://www.ebi.ac.uk/biostudies/studies/S-EPMC7992505biostudies-literatureUnknown26(5)Atypical teratoid/rhabdoid tumors (ATRTs) typically arise in the central nervous system (CNS) of children under 3 years of age. Despite intensive multimodal therapy (surgery, chemotherapy and, if age permits, radiotherapy), median survival is 17 months^1,2. We show that ATRTs robustly express B7-H3/CD276 that does not result from the inactivating mutations in SMARCB1 (refs. ^3,4), which drive oncogenesis in ATRT, but requires residual SWItch/Sucrose Non-Fermentable (SWI/SNF) activity mediated by BRG1/SMARCA4. Consistent with the embryonic origin of ATRT^5,6, B7-H3 is highly expressed on the prenatal, but not postnatal, brain. B7-H3.BB.z-chimeric antigen receptor (CAR) T cells administered intracerebroventricularly or intratumorally mediate potent antitumor effNature medicineLocoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors.PMC7992505P30 CA12443512-134R25 NS06574116/193Mount CWKool MFinetti MALabanieh LBourdeaut FDhingra SPfister SJohann PDWilliamson DTheruvath JZaidi SMackall CLSorensen PHXu PYecies DWDelaidelli AMajzner RGCheshier SGraef CMPuget SSotillo EHeitzeneder SLeruste AMitra SSHasselblatt MMueller SFruhwald MCMonje MSurdez DDelattre OfalseLocoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors.Atypical teratoid/rhabdoid tumors (ATRTs) typically arise in the central nervous system (CNS) of children under 3 years of age. Despite intensive multimodal therapy (surgery, chemotherapy and, if age permits, radiotherapy), median survival is 17 months^1,2. We show that ATRTs robustly express B7-H3/CD276 that does not result from the inactivating mutations in SMARCB1 (refs. ^3,4), which drive oncogenesis in ATRT, but requires residual SWItch/Sucrose Non-Fermentable (SWI/SNF) activity mediated by BRG1/SMARCA4. Consistent with the embryonic origin of ATRT^5,6, B7-H3 is highly expressed on the prenatal, but not postnatal, brain. B7-H3.BB.z-chimeric antigen receptor (CAR) T cells administered intracerebroventricularly or intratumorally mediate potent antitumor eff2020-01-01T00:00:00Z2020 May2026-05-02T11:27:07.85Z2025-04-05T17:16:28.16ZS-EPMC79925053234157910.1038/s41591-020-0821-8