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@ARTICLE{Charitidis:285061,
      author       = {F. T. Charitidis and E. Adabi and N. Ho and A. H. Braun$^*$
                      and C. Tierney and L. Strasser and F. B. Thalheimer and L.
                      Childs and J. Bones and C. Clarke and C. J. Buchholz$^*$},
      title        = {{CAR} {G}ene {D}elivery by {T}-cell {T}argeted {L}entiviral
                      {V}ectors is {E}nhanced by {R}apamycin {I}nduced {R}eduction
                      of {A}ntiviral {M}echanisms.},
      journal      = {Advanced science},
      volume       = {10},
      number       = {35},
      issn         = {2198-3844},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {DKFZ-2023-02204},
      pages        = {e2302992},
      year         = {2023},
      note         = {2023 Dec;10(35):e2302992},
      abstract     = {Lentiviral vectors (LV) have become the dominant tool for
                      stable gene transfer into lymphocytes including chimeric
                      antigen receptor (CAR) gene delivery to T cells, a major
                      breakthrough in cancer therapy. Yet, room for improvement
                      remains, especially for the latest LV generations delivering
                      genes selectively into T cell subtypes, a key requirement
                      for in vivo CAR T cell generation. Toward improving gene
                      transfer rates with these vectors, whole transcriptome
                      analyses on human T lymphocytes are conducted after exposure
                      to CAR-encoding conventional vectors (VSV-LV) and vectors
                      targeted to CD8+ (CD8-LV) or CD4+ T cells (CD4-LV). Genes
                      related to quiescence and antiviral restriction are found to
                      be upregulated in CAR-negative cells exposed to all types of
                      LVs. Down-modulation of various antiviral restriction
                      factors, including the interferon-induced transmembrane
                      proteins (IFITMs) is achieved with rapamycin as verified by
                      mass spectrometry (LC-MS). Strikingly, rapamycin enhances
                      transduction by up to 7-fold for CD8-LV and CD4-LV without
                      compromising CAR T cell activities but does not improve
                      VSV-LV. When administered to humanized mice, CD8-LV results
                      in higher rates of green fluorescent protein (GFP) gene
                      delivery. Also in vivo CAR T cell generation is improved in
                      kinetics and tumor control, however to a moderate extent,
                      leaving room for improvement by optimizing the rapamycin
                      administration schedule. The data favor multi-omics
                      approaches for improvements in gene delivery.},
      keywords     = {in vivo gene delivery (Other) / CAR T cells (Other) / IFITM
                      (Other) / rapamycin (Other) / receptor-targeted vectors
                      (Other) / scRNA-seq (Other) / transduction enhancer (Other)},
      cin          = {HD01 / FM01},
      ddc          = {624},
      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:37904721},
      doi          = {10.1002/advs.202302992},
      url          = {https://inrepo02.dkfz.de/record/285061},
}