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000154632 1001_ $$aTheruvath, Johanna$$b0
000154632 245__ $$aLocoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors.
000154632 260__ $$aNew York, NY$$bNature America Inc.$$c2020
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000154632 500__ $$a2020 May;26(5):712-719
000154632 520__ $$aAtypical 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 months1,2. 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 ATRT5,6, 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 effects against cerebral ATRT xenografts in mice, with faster kinetics, greater potency and reduced systemic levels of inflammatory cytokines compared to CAR T cells administered intravenously. CAR T cells administered ICV also traffic from the CNS into the periphery; following clearance of ATRT xenografts, B7-H3.BB.z-CAR T cells administered intracerebroventricularly or intravenously mediate antigen-specific protection from tumor rechallenge, both in the brain and periphery. These results identify B7-H3 as a compelling therapeutic target for this largely incurable pediatric tumor and demonstrate important advantages of locoregional compared to systemic delivery of CAR T cells for the treatment of CNS malignancies.
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000154632 7001_ $$aSotillo, Elena$$b1
000154632 7001_ $$aMount, Christopher W$$b2
000154632 7001_ $$aGraef, Claus Moritz$$b3
000154632 7001_ $$aDelaidelli, Alberto$$b4
000154632 7001_ $$aHeitzeneder, Sabine$$b5
000154632 7001_ $$aLabanieh, Louai$$b6
000154632 7001_ $$aDhingra, Shaurya$$b7
000154632 7001_ $$aLeruste, Amaury$$b8
000154632 7001_ $$aMajzner, Robbie G$$b9
000154632 7001_ $$aXu, Peng$$b10
000154632 7001_ $$aMueller, Sabine$$b11
000154632 7001_ $$00000-0001-8534-4651$$aYecies, Derek W$$b12
000154632 7001_ $$00000-0001-8173-1646$$aFinetti, Martina A$$b13
000154632 7001_ $$aWilliamson, Daniel$$b14
000154632 7001_ $$0P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8$$aJohann, Pascal D$$b15$$udkfz
000154632 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b16$$udkfz
000154632 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b17$$udkfz
000154632 7001_ $$aHasselblatt, Martin$$b18
000154632 7001_ $$aFrühwald, Michael C$$b19
000154632 7001_ $$aDelattre, Olivier$$b20
000154632 7001_ $$00000-0002-7118-7859$$aSurdez, Didier$$b21
000154632 7001_ $$aBourdeaut, Franck$$b22
000154632 7001_ $$aPuget, Stephanie$$b23
000154632 7001_ $$00000-0001-9128-0287$$aZaidi, Sakina$$b24
000154632 7001_ $$00000-0002-1829-7856$$aMitra, Siddhartha S$$b25
000154632 7001_ $$aCheshier, Samuel$$b26
000154632 7001_ $$aSorensen, Poul H$$b27
000154632 7001_ $$00000-0002-3547-237X$$aMonje, Michelle$$b28
000154632 7001_ $$00000-0001-6323-4304$$aMackall, Crystal L$$b29
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