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@ARTICLE{QuirosFernandez:276212,
      author       = {I. Quiros-Fernandez$^*$ and M. Poorebrahim$^*$ and F.
                      Marmé and S. E. Burdach and A. Cid-Arregui$^*$},
      title        = {{A} costimulatory chimeric antigen receptor targeting
                      {TROP}2 enhances the cytotoxicity of {NK} cells expressing a
                      {T} cell receptor reactive to human papillomavirus type 16
                      {E}7.},
      journal      = {Cancer letters},
      volume       = {566},
      issn         = {0304-3835},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2023-01024},
      pages        = {216242},
      year         = {2023},
      note         = {#EA:D122#LA:D122# / 2023 Jul 10;566:216242},
      abstract     = {Immune cells modified to express a tumor-reactive T cell
                      receptor (TCR) have shown limited efficacy as stand-alone
                      therapy against solid tumors. Genital and oropharyngeal
                      carcinomas induced by human papillomavirus (HPV) type 16
                      express constitutively its E6 and E7 oncoproteins, which
                      makes them convenient targets for adoptive cell
                      immunotherapy. However, viral antigen presentation by tumor
                      cells is low and limits the anti-tumor efficacy of CD8+ T
                      cells. To enhance the functionality of immune effector
                      cells, we have devised a strategy combining a costimulatory
                      chimeric antigen receptor (CAR) with a TCR. We used a
                      clinically tested TCR specific to E7 (E7-TCR) of HPV16 and a
                      newly constructed CAR targeting the trophoblast cell surface
                      antigen 2 (TROP2), which carried the intracellular
                      costimulatory domains CD28 and 4-1BB, but was devoid of the
                      CD3ζ domain. Flow cytometry analyses showed a notable
                      upregulation of activation markers and of cytolytic molecule
                      release by NK-92 cells genetically engineered to express
                      CD3, CD8 and both E7-TCR and TROP2-CAR, after co-incubation
                      with HPV16+ cervical cancer cells. Furthermore, the
                      E7-TCR/TROP2-CAR NK-92 cells demonstrated enhanced
                      antigen-specific activation and augmented cytotoxicity
                      against tumor cells compared with NK-92 cells expressing the
                      E7-TCR alone. A costimulatory TROP2-CAR can synergistically
                      cooperate with the E7-TCR in NK cells thereby enhancing
                      their signaling strength and antigen-specific cytotoxicity.
                      This approach might improve the outcome of adoptive cell
                      immunotherapies for HPV16+ cancer patients currently under
                      investigation.},
      keywords     = {Cervical cancer (Other) / Chimeric antigen receptor CAR
                      (Other) / Head and neck squamous cell carcinoma (Other) /
                      Human papillomavirus HPV (Other) / Natural killer cell NK
                      (Other) / T cell receptor TCR (Other) / TROP2 (Other)},
      cin          = {D122},
      ddc          = {570},
      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:37217069},
      doi          = {10.1016/j.canlet.2023.216242},
      url          = {https://inrepo02.dkfz.de/record/276212},
}