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@ARTICLE{Hemminki:126706,
      author       = {O. Hemminki and S. Parviainen and J. Juhila and R. Turkki
                      and N. Linder and J. Lundin and M. Kankainen and A.
                      Ristimäki and A. Koski and I. Liikanen and M. Oksanen and
                      D. Nettelbeck$^*$ and K. Kairemo and K. Partanen and T.
                      Joensuu and A. Kanerva and A. Hemminki},
      title        = {{I}mmunological data from cancer patients treated with
                      {A}d5/3-{E}2{F}-Δ24-{GMCSF} suggests utility for tumor
                      immunotherapy.},
      journal      = {OncoTarget},
      volume       = {6},
      number       = {6},
      issn         = {1949-2553},
      address      = {[S.l.]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2017-02734},
      pages        = {4467 - 4481},
      year         = {2015},
      abstract     = {Oncolytic viruses that selectively replicate in tumor cells
                      can be used for treatment of cancer. Accumulating data
                      suggests that virus induced oncolysis can enhance anti-tumor
                      immunity and break immune tolerance. To capitalize on the
                      immunogenic nature of oncolysis, we generated a quadruple
                      modified oncolytic adenovirus expressing
                      granulocyte-macrophage colony-stimulating factor (GMCSF).
                      Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a
                      tumor specific E2F1 promoter driving an E1 gene deleted at
                      the retinoblastoma protein binding site ('Δ24'). The fiber
                      features a knob from serotype 3 for enhanced gene delivery
                      to tumor cells. The virus was tested preclinically in vitro
                      and in vivo and then 13 patients with solid tumors
                      refractory to standard therapies were treated. Treatments
                      were well tolerated and frequent tumor- and
                      adenovirus-specific T-cell immune responses were seen.
                      Overall, with regard to tumor marker or radiological
                      responses, signs of antitumor efficacy were seen in 9/12
                      evaluable patients $(75\%).$ The radiological disease
                      control rate with positron emission tomography was $83\%$
                      while the response rate (including minor responses) was
                      $50\%.$ Tumor biopsies indicated accumulation of
                      immunological cells, especially T-cells, to tumors after
                      treatment. RNA expression analyses of tumors indicated
                      immunological activation and metabolic changes secondary to
                      virus replication.},
      keywords     = {Antibodies, Neutralizing (NLM Chemicals) / Antibodies,
                      Viral (NLM Chemicals) / E2F1 Transcription Factor (NLM
                      Chemicals) / E2F1 protein, human (NLM Chemicals) /
                      Granulocyte-Macrophage Colony-Stimulating Factor (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:25714011},
      pmc          = {pmc:PMC4414204},
      doi          = {10.18632/oncotarget.2901},
      url          = {https://inrepo02.dkfz.de/record/126706},
}