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@ARTICLE{MuraliShankar:285001,
      author       = {N. Murali Shankar and P. Ortiz-Montero and A. Kurzyukova
                      and W. Rackwitz and S. R. Künzel and W. S. Wels$^*$ and T.
                      Tonn$^*$ and F. Knopf and J. Eitler},
      title        = {{P}reclinical assessment of {CAR}-{NK} cell-mediated
                      killing efficacy and pharmacokinetics in a rapid zebrafish
                      xenograft model of metastatic breast cancer.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-02174},
      pages        = {1254821},
      year         = {2023},
      abstract     = {Natural killer (NK) cells are attractive effectors for
                      adoptive immunotherapy of cancer. Results from
                      first-in-human studies using chimeric antigen receptor
                      (CAR)-engineered primary NK cells and NK-92 cells are
                      encouraging in terms of efficacy and safety. In order to
                      further improve treatment strategies and to test the
                      efficacy of CAR-NK cells in a personalized manner,
                      preclinical screening assays using patient-derived tumor
                      samples are needed. Zebrafish (Danio rerio) embryos and
                      larvae represent an attractive xenograft model to study
                      growth and dissemination of patient-derived tumor cells
                      because of their superb live cell imaging properties.
                      Injection into the organism's circulation allows
                      investigation of metastasis, cancer cell-to-immune
                      cell-interactions and studies of the tumor cell response to
                      anti-cancer drugs. Here, we established a zebrafish larval
                      xenograft model to test the efficacy of CAR-NK cells against
                      metastatic breast cancer in vivo by injecting metastatic
                      breast cancer cells followed by CAR-NK cell injection into
                      the Duct of Cuvier (DoC). We validated the functionality of
                      the system with two different CAR-NK cell lines specific for
                      PD-L1 and ErbB2 (PD-L1.CAR NK-92 and ErbB2.CAR NK-92 cells)
                      against the PD-L1-expressing MDA-MB-231 and ErbB2-expressing
                      MDA-MB-453 breast cancer cell lines. Injected cancer cells
                      were viable and populated peripheral regions of the larvae,
                      including the caudal hematopoietic tissue (CHT), simulating
                      homing of cancer cells to blood forming sites. CAR-NK cells
                      injected 2.5 hours later migrated to the CHT and rapidly
                      eliminated individual cancer cells throughout the organism.
                      Unmodified NK-92 also demonstrated minor in vivo
                      cytotoxicity. Confocal live-cell imaging demonstrated
                      intravascular migration and real-time interaction of CAR-NK
                      cells with MDA-MB-231 cells, explaining the rapid and
                      effective in vivo cytotoxicity. Thus, our data suggest that
                      zebrafish larvae can be used for rapid and cost-effective in
                      vivo assessment of CAR-NK cell potency and to predict
                      patient response to therapy.},
      keywords     = {CAR-NK cells (Other) / ErbB2 (HER2) (Other) / NK-92 (Other)
                      / PD-L1 (Other) / breast cancer (Other) / cancer
                      immunotherapy (Other) / in vivo imaging (Other) / zebrafish
                      xenograft (Other)},
      cin          = {FM01 / DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331 / I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37885894},
      pmc          = {pmc:PMC10599014},
      doi          = {10.3389/fimmu.2023.1254821},
      url          = {https://inrepo02.dkfz.de/record/285001},
}