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@ARTICLE{Soto:286660,
author = {K. E. G. Soto and L. R. Loureiro and T. Bartsch and C.
Arndt and A. Kegler and N. Mitwasi and L. Drewitz and L.
Hoffmann and H. A. Saleh and E. Crespo and M. Mehnert and C.
Daglar and H. Abken and F. Momburg$^*$ and M. Bachmann$^*$
and A. Feldmann$^*$},
title = {{T}argeting colorectal cancer cells using {AND}-gated
adaptor {R}ev{CAR} {T}-cells.},
journal = {Frontiers in immunology},
volume = {14},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2024-00024},
pages = {1302354},
year = {2023},
abstract = {Despite the success of chimeric antigen receptor (CAR)
T-cells especially for treating hematological malignancies,
critical drawbacks, such as 'on-target, off-tumor'
toxicities, need to be addressed to improve safety in
translating to clinical application. This is especially
true, when targeting tumor-associated antigens (TAAs) that
are not exclusively expressed by solid tumors but also on
hea9lthy tissues. To improve the safety profile, we
developed switchable adaptor CAR systems including the
RevCAR system. RevCAR T-cells are activated by cross-linking
of bifunctional adaptor molecules termed target modules
(RevTM). In a further development, we established a
Dual-RevCAR system for an AND-gated combinatorial targeting
by splitting the stimulatory and co-stimulatory signals of
the RevCAR T-cells on two individual CARs. Examples of
common markers for colorectal cancer (CRC) are the
carcinoembryonic antigen (CEA) and the epithelial cell
adhesion molecule (EpCAM), while these antigens are also
expressed by healthy cells. Here we describe four novel
structurally different RevTMs for targeting of CEA and
EpCAM. All anti-CEA and anti-EpCAM RevTMs were validated and
the simultaneous targeting of CEA+ and EpCAM+ cancer cells
redirected specific in vitro and in vivo killing by
Dual-RevCAR T-cells. In summary, we describe the development
of CEA and EpCAM specific adaptor RevTMs for monospecific
and AND-gated targeting of CRC cells via the RevCAR platform
as an improved approach to increase tumor specificity and
safety of CAR T-cell therapies.},
keywords = {AND-gate targeting (Other) / CAR T-cells (Other) / CEA
(Other) / EpCAM (Other) / colorectal cancer (Other)},
cin = {DD01 / D121},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331 / I:(DE-He78)D121-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38169746},
pmc = {pmc:PMC10758449},
doi = {10.3389/fimmu.2023.1302354},
url = {https://inrepo02.dkfz.de/record/286660},
}