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@ARTICLE{Kapitza:282426,
      author       = {L. Kapitza$^*$ and N. Ho and T. Kerzel and A. M. Frank and
                      F. B. Thalheimer and A. Jamali and T. Schaser and C. J.
                      Buchholz$^*$ and J. Hartmann},
      title        = {{CD}62{L} as target receptor for specific gene delivery
                      into less differentiated human {T} lymphocytes.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-01753},
      pages        = {1183698},
      year         = {2023},
      abstract     = {Chimeric antigen receptor (CAR)-expressing T cells are a
                      complex and heterogeneous gene therapy product with variable
                      phenotype compositions. A higher proportion of less
                      differentiated CAR T cells is usually associated with
                      improved antitumoral function and persistence. We describe
                      in this study a novel receptor-targeted lentiviral vector
                      (LV) named 62L-LV that preferentially transduces less
                      differentiated T cells marked by the L-selectin receptor
                      CD62L, with transduction rates of up to $70\%$ of CD4+ and
                      $50\%$ of CD8+ primary T cells. Remarkably, higher amounts
                      of less differentiated T cells are transduced and preserved
                      upon long-term cultivation using 62L-LV compared to VSV-LV.
                      Interestingly, shed CD62L neither altered the binding of
                      62L-LV particles to T cells nor impacted their transduction.
                      The incubation of 2 days of activated T lymphocytes with
                      62L-LV or VSV-LV for only 24 hours was sufficient to
                      generate CAR T cells that controlled tumor growth in a
                      leukemia tumor mouse model. The data proved that potent CAR
                      T cells can be generated by short-term ex vivo exposure of
                      primary cells to LVs. As a first vector type that
                      preferentially transduces less differentiated T lymphocytes,
                      62L-LV has the potential to circumvent cumbersome selections
                      of T cell subtypes and offers substantial shortening of the
                      CAR T cell manufacturing process.},
      keywords     = {CAR T cells (Other) / L-selectin (Other) / LV (Other) /
                      chimeric antigen receptor (Other) / naïve T lymphocytes
                      (Other) / receptor-targeted viral vectors (Other) / ΔLNGFR
                      (Other)},
      cin          = {HD01 / FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)HD01-20160331 / I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37646032},
      pmc          = {pmc:PMC10461316},
      doi          = {10.3389/fimmu.2023.1183698},
      url          = {https://inrepo02.dkfz.de/record/282426},
}