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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},
}