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@ARTICLE{Saleh:275757,
author = {H. A. Saleh and N. Mitwasi and M. Ullrich and M. Kubeil and
M. Toussaint and W. Deuther-Conrad and C. Neuber and C.
Arndt and L. R Loureiro and A. Kegler and K. E. González
Soto and B. Belter and C. Rössig and J. Pietzsch and M.
Frenz and M. Bachmann$^*$ and A. Feldmann$^*$},
title = {{S}pecific and safe targeting of glioblastoma using
switchable and logic-gated {R}ev{CAR} {T} cells.},
journal = {Frontiers in immunology},
volume = {14},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-00856},
pages = {1166169},
year = {2023},
abstract = {Glioblastoma (GBM) is still an incurable tumor that is
associated with high recurrence rate and poor survival
despite the current treatment regimes. With the urgent need
for novel therapeutic strategies, immunotherapies,
especially chimeric antigen receptor (CAR)-expressing T
cells, represent a promising approach for specific and
effective targeting of GBM. However, CAR T cells can be
associated with serious side effects. To overcome such
limitation, we applied our switchable RevCAR system to
target both the epidermal growth factor receptor (EGFR) and
the disialoganglioside GD2, which are expressed in GBM. The
RevCAR system is a modular platform that enables
controllability, improves safety, specificity and
flexibility. Briefly, it consists of RevCAR T cells having a
peptide epitope as extracellular domain, and a bispecific
target module (RevTM). The RevTM acts as a switch key that
recognizes the RevCAR epitope and the tumor-associated
antigen, and thereby activating the RevCAR T cells to kill
the tumor cells. However, in the absence of the RevTM, the
RevCAR T cells are switched off. In this study, we show that
the novel EGFR/GD2-specific RevTMs can selectively activate
RevCAR T cells to kill GBM cells. Moreover, we show that
gated targeting of GBM is possible with our Dual-RevCAR T
cells, which have their internal activation and
co-stimulatory domains separated into two receptors.
Therefore, a full activation of Dual-RevCAR T cells can only
be achieved when both receptors recognize EGFR and GD2
simultaneously via RevTMs, leading to a significant killing
of GBM cells both in vitro and in vivo.},
keywords = {CAR T cells (Other) / adaptor CAR platform (Other) /
combinatorial gated targeting (Other) / glioblastoma (Other)
/ immunotherapy (Other)},
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:37122703},
pmc = {pmc:PMC10145173},
doi = {10.3389/fimmu.2023.1166169},
url = {https://inrepo02.dkfz.de/record/275757},
}