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000298625 1001_ $$00009-0001-2798-8878$$aCrespo, Eugenia$$b0
000298625 245__ $$aRevCAR-mediated T-cell response against PD-L1-expressing cells turns suppression into activation.
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000298625 520__ $$aApplying CAR T-cell therapy to treat solid tumors is especially challenging due to the immunosuppressive tumor microenvironment (TME). While our modular RevCAR system enhances the safety and controllability of CAR T-cell therapy, effectively targeting solid tumors remains difficult. Since PD-L1 is an immune checkpoint frequently upregulated by cancer cells and their microenvironment, it is a relevant target for solid tumors. Here, we introduce a novel PD-L1 RevTM capable of redirecting RevCAR T-cells to specifically target and kill PD-L1-expressing tumor cells, becoming activated and secreting pro-inflammatory cytokines. This is shown in vitro with monolayer and 3D models, including patient-derived cultures, and in vivo. Furthermore, we demonstrate in vitro and in vivo an AND-gated targeting of cells simultaneously expressing PD-L1 and another tumor-associated antigen by the Dual RevCAR system. Our findings suggest that RevCAR-mediated targeting of PD-L1 could be a promising therapeutic approach for modulating the TME and improving solid tumor treatment.
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000298625 7001_ $$aLoureiro, Liliana R$$b1
000298625 7001_ $$00009-0005-1280-967X$$aStammberger, Antonia$$b2
000298625 7001_ $$aHoffmann, Lydia$$b3
000298625 7001_ $$aBerndt, Nicole$$b4
000298625 7001_ $$aHoffmann, Anja$$b5
000298625 7001_ $$aDagostino, Claudia$$b6
000298625 7001_ $$aSoto, Karla E G$$b7
000298625 7001_ $$aRupp, Luise$$b8
000298625 7001_ $$aArndt, Claudia$$b9
000298625 7001_ $$aSchneider, Martin$$b10
000298625 7001_ $$0P:(DE-He78)7a10ea1b9b2872da9f375002c44ddfce$$aBall, Claudia$$b11
000298625 7001_ $$0P:(DE-HGF)0$$aBachmann, Michael$$b12
000298625 7001_ $$0P:(DE-HGF)0$$aSchmitz, Marc$$b13
000298625 7001_ $$00000-0001-5099-2448$$aFeldmann, Anja$$b14
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