% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Ebrahimi:303478,
      author       = {S. Ebrahimi and B. J. Lohnes and S. A. Khan and M. Peipp
                      and E. Bockamp$^*$ and C. Klein and H. Abken and C.
                      Wölfel$^*$ and M. Theobald$^*$ and U. F. Hartwig$^*$},
      title        = {{T}argeting mutated {KRAS} by {HLA}-{A}*02:01 restricted
                      anti-{KRAS} {TCR}-mimic {CAR} and bispecific {T} cell
                      engager.},
      journal      = {Journal of molecular medicine},
      volume       = {103},
      number       = {10},
      issn         = {0023-2173},
      address      = {New York, NY},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-01675},
      pages        = {1231-1246},
      year         = {2025},
      note         = {2025 Oct;103(10):1231-1246},
      abstract     = {Mutations in the KRAS proto-oncogene, particularly at codon
                      12, are among the most frequent genetic alterations in
                      various cancers, and KRASG12V accounts for about $25\%$ of
                      all KRAS mutations observed in lung, pancreatic, and
                      colorectal adenocarcinomas. Despite improved treatment
                      regimes using targeted therapy and checkpoint inhibitors,
                      cellular immunotherapy options for KRAS-mutated cancers
                      remain elusive. We therefore developed two TCR-mimic (TCRm)
                      anti-KRASG12V/HLA-A*02:01 chimeric antigen receptors (CARs)
                      containing different hinge regions and, alternatively, a
                      TCRm anti-KRASG12V/HLA-A*02:01 bispecific T cell engager
                      (BiTE) to explore immunotherapy to the highly prevalent
                      KRASG12V neoantigen. CAR-redirected or BiTE-exposed
                      JNL-reporter cells demonstrated potent signaling capacity
                      upon recognition of KRASG12V. Moreover, human CAR T and NK
                      cells elicited IFN-γ release and cellular cytotoxicity upon
                      encountering target cells pulsed with KRASG12V peptide, and
                      the anti-KRASG12V Strep-tagII hinge CAR showed superior
                      reactivity compared to a human IgG1-Fc hinge CAR. Similarly,
                      a novel TCRm BiTE induced strong T cell immunity to
                      KRASG12V. In contrast, we observed only very low CAR or
                      BITE-mediated responses to naturally presented
                      KRASG12V/HLA-A*02:01 complexes. In summary, this study
                      demonstrates that the mutation-derived KRASG12V5-14 peptide
                      can be effectively targeted by TCRm CAR and BiTE-redirected
                      T cells, suggesting that TCRm anti-KRASG12V CAR or BiTE
                      represent promising formats to advance immunotherapy to
                      mutated KRAS neoepitopes. KEY MESSAGES: Successful
                      development of TCRm CAR and BiTE targeting mutated
                      KRAS/HLA-A*02:01. Anti-KRASG12V TCRm CAR and BiTE induce
                      potent immunity to KRASG12V neoepitope. Anti-KRAS/HLA-I TCRm
                      CARs and BiTEs are novel therapeutics for cancer
                      immunotherapy.},
      keywords     = {Chimeric antigen receptor (Other) / Immunotherapy (Other) /
                      KRAS neoepitopes (Other) / T cell therapy (Other) /
                      TCR-mimic CAR (Other) / TCR-mimic bispecific antibody
                      (Other)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40794198},
      doi          = {10.1007/s00109-025-02585-2},
      url          = {https://inrepo02.dkfz.de/record/303478},
}