TY  - JOUR
AU  - Crespo, Eugenia
AU  - Loureiro, Liliana R
AU  - Stammberger, Antonia
AU  - Hoffmann, Lydia
AU  - Berndt, Nicole
AU  - Hoffmann, Anja
AU  - Dagostino, Claudia
AU  - Soto, Karla E G
AU  - Rupp, Luise
AU  - Arndt, Claudia
AU  - Schneider, Martin
AU  - Ball, Claudia
AU  - Bachmann, Michael
AU  - Schmitz, Marc
AU  - Feldmann, Anja
TI  - RevCAR-mediated T-cell response against PD-L1-expressing cells turns suppression into activation.
JO  - npj precision oncology
VL  - 9
IS  - 1
SN  - 2397-768X
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00325
SP  - 42
PY  - 2025
AB  - Applying 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:39924591
DO  - DOI:10.1038/s41698-025-00828-6
UR  - https://inrepo02.dkfz.de/record/298625
ER  -