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@ARTICLE{Knippertz:128915,
      author       = {I. Knippertz and A. Deinzer and J. Dörrie and N. Schaft
                      and D. M. Nettelbeck$^*$ and A. Steinkasserer},
      title        = {{T}ranscriptional {T}argeting of {M}ature {D}endritic
                      {C}ells with {A}denoviral {V}ectors via a {M}odular
                      {P}romoter {S}ystem for {A}ntigen {E}xpression and
                      {F}unctional {M}anipulation.},
      journal      = {Journal of Immunology Research},
      volume       = {2016},
      issn         = {2314-7156},
      address      = {New York, NY},
      publisher    = {Hindawi},
      reportid     = {DKFZ-2017-04928},
      pages        = {1 - 17},
      year         = {2016},
      abstract     = {To specifically target dendritic cells (DCs) to
                      simultaneously express different therapeutic transgenes for
                      inducing immune responses against tumors, we used a combined
                      promoter system of adenoviral vectors. We selected a
                      216 bp short Hsp70B' core promoter induced by a mutated,
                      constitutively active heat shock factor (mHSF) 1 to drive
                      strong gene expression of therapeutic transgenes MelanA,
                      BclxL, and IL-12p70 in HeLa cells, as well as in mature DCs
                      (mDCs). As this involves overexpressing mHSF1, we first
                      evaluated the resulting effects on DCs regarding
                      upregulation of heat shock proteins and maturation markers,
                      toxicity, cytokine profile, and capacity to induce
                      antigen-specific CD8(+) T cells. Second, we generated the
                      two-vector-based 'modular promoter' system, where one vector
                      contains the mHSF1 under the control of the human CD83
                      promoter, which is specifically active only in DCs and after
                      maturation. mHSF1, in turn, activates the Hsp70B' core
                      promotor-driven expression of transgenes MelanA and IL-12p70
                      in the DC-like cell line XS52 and in human mature and hence
                      immunogenic DCs, but not in tolerogenic immature DCs. These
                      in vitro experiments provide the basis for an in vivo
                      targeting of mature DCs for the expression of multiple
                      transgenes. Therefore, this modular promoter system
                      represents a promising tool for future DC-based
                      immunotherapies in vivo.},
      keywords     = {Antigens, CD (NLM Chemicals) / BCL2L1 protein, human (NLM
                      Chemicals) / CD83 antigen (NLM Chemicals) / Cytokines (NLM
                      Chemicals) / DNA-Binding Proteins (NLM Chemicals) /
                      Immunoglobulins (NLM Chemicals) / MART-1 Antigen (NLM
                      Chemicals) / Membrane Glycoproteins (NLM Chemicals) /
                      Transcription Factors (NLM Chemicals) / bcl-X Protein (NLM
                      Chemicals) / heat shock transcription factor (NLM Chemicals)
                      / Interleukin-12 (NLM Chemicals)},
      cin          = {F110},
      ddc          = {610},
      cid          = {I:(DE-He78)F110-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27446966},
      pmc          = {pmc:PMC4942663},
      doi          = {10.1155/2016/6078473},
      url          = {https://inrepo02.dkfz.de/record/128915},
}