% 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{Silvestre:284631,
      author       = {R. N. Silvestre and J. Eitler and J. T. C. de Azevedo and
                      M. C. Tirapelle and D. M. C. Fantacini and L. E. B. de Souza
                      and K. Swiech and D. T. Covas and R. T. Calado and P. O.
                      Montero and K. C. R. Malmegrim and M. L. Figueiredo and T.
                      Tonn$^*$ and V. Picanço-Castro},
      title        = {{E}ngineering {NK}-{CAR}.19 cells with the
                      {IL}-15/{IL}-15{R}α complex improved proliferation and
                      anti-tumor effect in vivo.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-02038},
      pages        = {1226518},
      year         = {2023},
      abstract     = {Natural killer 92 (NK-92) cells are an attractive
                      therapeutic approach as alternative chimeric antigen
                      receptor (CAR) carriers, different from T cells, once they
                      can be used in the allogeneic setting. The modest in vivo
                      outcomes observed with NK-92 cells continue to present
                      hurdles in successfully translating NK-92 cell therapies
                      into clinical applications. Adoptive transfer of CAR-NK-92
                      cells holds out the promise of therapeutic benefit at a
                      lower rate of adverse events due to the absence of GvHD and
                      cytokine release syndrome. However, it has not achieved
                      breakthrough clinical results yet, and further improvement
                      of CAR-NK-92 cells is necessary.In this study, we conducted
                      a comparative analysis between CD19-targeted CAR (CAR.19)
                      co-expressing IL-15 (CAR.19-IL15) with IL-15/IL-15Rα
                      (CAR.19-IL15/IL15Rα) to promote NK cell proliferation,
                      activation, and cytotoxic activity against B-cell leukemia.
                      CAR constructs were cloned into lentiviral vector and
                      transduced into NK-92 cell line. Potency of CAR-NK cells
                      were assessed against CD19-expressing cell lines NALM-6 or
                      Raji in vitro and in vivo in a murine model. Tumor burden
                      was measured by bioluminescence.We demonstrated that a
                      fourth- generation CD19-targeted CAR (CAR.19) co-expressing
                      IL-15 linked to its receptor IL-15/IL-15Rα
                      (CAR.19-IL-15/IL-15Rα) significantly enhanced NK-92 cell
                      proliferation, proinflammatory cytokine secretion, and
                      cytotoxic activity against B-cell cancer cell lines in vitro
                      and in a xenograft mouse model.Together with the results of
                      the systematic analysis of the transcriptome of activated
                      NK-92 CAR variants, this supports the notion that
                      IL-15/IL-15Rα comprising fourth-generation CARs may
                      overcome the limitations of NK-92 cell-based targeted tumor
                      therapies in vivo by providing the necessary growth and
                      activation signals.},
      keywords     = {B-cell malignances (Other) / CAR-NK cells (Other) / IL-15
                      (Other) / IL-15 receptor (Other) / NK-92 (Other) / adoptive
                      cell therapy (Other) / allogeneic therapy (Other)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37818365},
      pmc          = {pmc:PMC10561086},
      doi          = {10.3389/fimmu.2023.1226518},
      url          = {https://inrepo02.dkfz.de/record/284631},
}