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@ARTICLE{Foldvari:278732,
      author       = {Z. Foldvari and C. Knetter and W. Yang and T. J. Gjerdingen
                      and R. C. Bollineni and T. T. Tran and F. Lund-Johansen and
                      A. Kolstad and K. Drousch and R. Klopfleisch and M.
                      Leisegang$^*$ and J. Olweus},
      title        = {{A} systematic safety pipeline for selection of {T}-cell
                      receptors to enter clinical use.},
      journal      = {npj vaccines},
      volume       = {8},
      number       = {1},
      issn         = {2059-0105},
      address      = {[London]},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2023-01703},
      pages        = {126},
      year         = {2023},
      abstract     = {Cancer immunotherapy using T cell receptor-engineered T
                      cells (TCR-Ts) represents a promising treatment option.
                      However, technologies for pre-clinical safety assessment are
                      incomplete or inaccessible to most laboratories. Here, TCR-T
                      off-target reactivity was assessed in five steps: (1)
                      Mapping target amino acids necessary for TCR-T recognition,
                      followed by (2) a computational search for, and (3)
                      reactivity screening against, candidate cross-reactive
                      peptides in the human proteome. Natural processing and
                      presentation of recognized peptides was evaluated using (4)
                      short mRNAs, and (5) full-length proteins. TCR-Ts were
                      screened for recognition of unintended HLA alleles, and as
                      proxy for off-target reactivity in vivo, a syngeneic,
                      HLA-A*02:01-transgenic mouse model was used. Validation
                      demonstrated importance of studying recognition of
                      full-length candidate off-targets, and that the clinically
                      applied 1G4 TCR has a hitherto unknown reactivity to
                      unintended HLA alleles, relevant for patient selection. This
                      widely applicable strategy should facilitate evaluation of
                      candidate therapeutic TCRs and inform clinical
                      decision-making.},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37607971},
      doi          = {10.1038/s41541-023-00713-y},
      url          = {https://inrepo02.dkfz.de/record/278732},
}