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@ARTICLE{VelascoCrdenas:285256,
      author       = {R. M. Velasco Cárdenas and S. M. Brandl and A. V.
                      Meléndez and A. E. Schlaak and A. Buschky and T. Peters and
                      F. Beier and B. Serrels and S. Taromi and K. Raute and S.
                      Hauri and M. Gstaiger and S. Lassmann and J. B. Huppa and M.
                      Börries$^*$ and G. Andrieux and B. Bengsch and W. W.
                      Schamel and S. Minguet},
      title        = {{H}arnessing {CD}3 diversity to optimize {CAR} {T} cells.},
      journal      = {Nature immunology},
      volume       = {24},
      number       = {12},
      issn         = {1529-2908},
      address      = {London},
      publisher    = {Springer Nature Limited},
      reportid     = {DKFZ-2023-02291},
      pages        = {2135-2149},
      year         = {2023},
      note         = {2023 Dec;24(12):2135-2149},
      abstract     = {Current US Food and Drug Administration-approved chimeric
                      antigen receptor (CAR) T cells harbor the T cell receptor
                      (TCR)-derived ζ chain as an intracellular activation domain
                      in addition to costimulatory domains. The functionality in a
                      CAR format of the other chains of the TCR complex, namely
                      CD3δ, CD3ε and CD3γ, instead of ζ, remains unknown. In
                      the present study, we have systematically engineered new CD3
                      CARs, each containing only one of the CD3 intracellular
                      domains. We found that CARs containing CD3δ, CD3ε or CD3γ
                      cytoplasmic tails outperformed the conventional ζ CAR T
                      cells in vivo. Transcriptomic and proteomic analysis
                      revealed differences in activation potential, metabolism and
                      stimulation-induced T cell dysfunctionality that
                      mechanistically explain the enhanced anti-tumor performance.
                      Furthermore, dimerization of the CARs improved their overall
                      functionality. Using these CARs as minimalistic and
                      synthetic surrogate TCRs, we have identified the phosphatase
                      SHP-1 as a new interaction partner of CD3δ that binds the
                      CD3δ-ITAM on phosphorylation of its C-terminal tyrosine.
                      SHP-1 attenuates and restrains activation signals and might
                      thus prevent exhaustion and dysfunction. These new insights
                      into T cell activation could promote the rational redesign
                      of synthetic antigen receptors to improve cancer
                      immunotherapy.},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37932456},
      doi          = {10.1038/s41590-023-01658-z},
      url          = {https://inrepo02.dkfz.de/record/285256},
}