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@ARTICLE{QuirosFernandez:289779,
      author       = {I. Quiros-Fernandez$^*$ and S. Libório-Ramos$^*$ and L.
                      Leifert$^*$ and B. Schönfelder$^*$ and I. Vlodavsky and A.
                      Cid-Arregui$^*$},
      title        = {{D}ual {T} cell receptor/chimeric antigen receptor
                      engineered {NK}-92 cells targeting the {HPV}16 {E}6
                      oncoprotein and the tumor-associated antigen {L}1{CAM}
                      exhibit enhanced cytotoxicity and specificity against tumor
                      cells.},
      journal      = {Journal of medical virology},
      volume       = {96},
      number       = {5},
      issn         = {0146-6615},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley},
      reportid     = {DKFZ-2024-00858},
      pages        = {e29630},
      year         = {2024},
      note         = {#EA:D122#LA:D122#},
      abstract     = {The human papillomavirus type 16 (HPV16) causes a large
                      fraction of genital and oropharyngeal carcinomas. To
                      maintain the transformed state, the tumor cells must
                      continuously synthesize the E6 and E7 viral oncoproteins,
                      which makes them tumor-specific antigens. Indeed, specific T
                      cell responses against them have been well documented and
                      CD8+ T cells engineered to express T cell receptors (TCRs)
                      that recognize epitopes of E6 or E7 have been tested in
                      clinical studies with promising results, yet with limited
                      clinical success. Using CD8+ T cells from peripheral blood
                      of healthy donors, we have identified two novel TCRs
                      reactive to an unexplored E618-26 epitope. These TCRs showed
                      limited standalone cytotoxicity against
                      E618-26-HLA-A*02:01-presenting tumor cells. However, a
                      single-signaling domain chimeric antigen receptor (ssdCAR)
                      targeting L1CAM, a cell adhesion protein frequently
                      overexpressed in HPV16-induced cancer, prompted a
                      synergistic effect that significantly enhanced the cytotoxic
                      capacity of NK-92/CD3/CD8 cells armored with both TCR and
                      ssdCAR when both receptors simultaneously engaged their
                      respective targets, as shown by live microscopy of 2-D and
                      3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T
                      cell repertoire of healthy donors can be combined with a
                      suitable ssdCAR to enhance the cytotoxic capacity of the
                      effector cells and, indirectly, their specificity.},
      keywords     = {Humans / Oncogene Proteins, Viral: immunology / Oncogene
                      Proteins, Viral: genetics / Receptors, Chimeric Antigen:
                      immunology / Receptors, Chimeric Antigen: genetics /
                      Receptors, Antigen, T-Cell: immunology / Receptors, Antigen,
                      T-Cell: genetics / Repressor Proteins: immunology /
                      Repressor Proteins: genetics / CD8-Positive T-Lymphocytes:
                      immunology / Killer Cells, Natural: immunology / Human
                      papillomavirus 16: immunology / Human papillomavirus 16:
                      genetics / Cytotoxicity, Immunologic / Cell Line, Tumor /
                      CAR (Other) / T cell receptor (Other) / adoptive cell
                      transfer (Other) / cell therapy (Other) / cervical cancer
                      (Other) / chimeric antigen receptor (Other) / human
                      papillomavirus (Other) / immunotherapy (Other) / Oncogene
                      Proteins, Viral (NLM Chemicals) / E6 protein, Human
                      papillomavirus type 16 (NLM Chemicals) / Receptors, Chimeric
                      Antigen (NLM Chemicals) / Receptors, Antigen, T-Cell (NLM
                      Chemicals) / Repressor Proteins (NLM Chemicals)},
      cin          = {D122},
      ddc          = {610},
      cid          = {I:(DE-He78)D122-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38659368},
      doi          = {10.1002/jmv.29630},
      url          = {https://inrepo02.dkfz.de/record/289779},
}