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@ARTICLE{Crespo:298625,
author = {E. Crespo and L. R. Loureiro and A. Stammberger and L.
Hoffmann and N. Berndt and A. Hoffmann and C. Dagostino and
K. E. G. Soto and L. Rupp and C. Arndt and M. Schneider and
C. Ball$^*$ and M. Bachmann$^*$ and M. Schmitz$^*$ and A.
Feldmann$^*$},
title = {{R}ev{CAR}-mediated {T}-cell response against
{PD}-{L}1-expressing cells turns suppression into
activation.},
journal = {npj precision oncology},
volume = {9},
number = {1},
issn = {2397-768X},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-00325},
pages = {42},
year = {2025},
abstract = {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.},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39924591},
doi = {10.1038/s41698-025-00828-6},
url = {https://inrepo02.dkfz.de/record/298625},
}