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@ARTICLE{Immisch:274139,
      author       = {L. Immisch$^*$ and G. Papafotiou$^*$ and N. Gallarín
                      Delgado and V. Scheuplein and A. Paschen$^*$ and T.
                      Blankenstein and G. Willimsky$^*$},
      title        = {{T}argeting the recurrent {R}ac1{P}29{S} neoepitope in
                      melanoma with heterologous high-affinity {T} cell
                      receptors.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-00449},
      pages        = {1119498},
      year         = {2023},
      abstract     = {Recurrent neoepitopes are cancer-specific antigens common
                      among groups of patients and therefore ideal targets for
                      adoptive T cell therapy. The neoepitope FSGEYIPTV carries
                      the Rac1P29S amino acid change caused by a c.85C>T missense
                      mutation, which is the third most common hotspot mutation in
                      melanoma. Here, we isolated and characterized TCRs to target
                      this HLA-A*02:01-binding neoepitope by adoptive T cell
                      therapy. Peptide immunization elicited immune responses in
                      transgenic mice expressing a diverse human TCR repertoire
                      restricted to HLA-A*02:01, which enabled isolation of
                      high-affinity TCRs. TCR-transduced T cells induced
                      cytotoxicity against Rac1P29S expressing melanoma cells and
                      we observed regression of Rac1P29S expressing tumors in vivo
                      after adoptive T cell therapy (ATT). Here we found that a
                      TCR raised against a heterologous mutation with higher
                      peptide-MHC affinity (Rac2P29L) more efficiently targeted
                      the common melanoma mutation Rac1P29S. Overall, our study
                      provides evidence for the therapeutic potential of
                      Rac1P29S-specific TCR-transduced T cells and reveal a novel
                      strategy by generating more efficient TCRs by heterologous
                      peptides.},
      keywords     = {Rho (Rho GTPase) (Other) / TCR gene therapy (Other) /
                      humanized mouse models (Other) / melanoma (Other) /
                      neoantigen (Other)},
      cin          = {BE01 / ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36875127},
      pmc          = {pmc:PMC9978334},
      doi          = {10.3389/fimmu.2023.1119498},
      url          = {https://inrepo02.dkfz.de/record/274139},
}