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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},
}