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@ARTICLE{GarciaMoure:166637,
      author       = {M. Garcia-Moure and M. Gonzalez-Huarriz and S. Labiano and
                      E. Guruceaga and E. Bandres and M. Zalacain and L. Marrodan
                      and C. E. de Andrea and M. Villalba Esparza and N.
                      Martínez-Vélez and V. Laspidea and M. Puigdelloses and J.
                      Gallego Perez-Larraya and I. Iñigo-Marco and R. Stripecke
                      and J. A. Chan and E. H. Raabe and M. Kool$^*$ and C.
                      Gomez-Manzano and J. Fueyo and A. Patiño-García and M. M.
                      Alonso},
      title        = {{D}elta-24-{RGD}, an oncolytic adenovirus, increases
                      survival and promotes proinflammatory immune landscape
                      remodeling in models of {AT}/{RT} and {CNS}-{PNET}.},
      journal      = {Clinical cancer research},
      volume       = {27},
      number       = {6},
      issn         = {1557-3265},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2021-00004},
      pages        = {1807-1820},
      year         = {2021},
      note         = {2021 Mar 15;27(6):1807-1820},
      abstract     = {Atypical teratoid/rhabdoid tumors (AT/RTs) and primitive
                      neuroectodermal tumors (CNS-PNETs) are pediatric brain
                      tumors with poor survival and life-long negative side
                      effects. Here, the aim was to characterize the efficacy and
                      safety of the oncolytic adenovirus Delta-24-RGDs, which
                      selectively replicates in and kills tumor cells.Delta-24-RGD
                      determinants for infection and replication were evaluated in
                      patient expression data sets. Viral replication and
                      cytotoxicity were assessed invitro in a battery of CNS-PNET
                      and AT/RT cell lines. In vivo, efficacy was determined in
                      different orthotopic mouse models, including early and
                      established tumor models, a disseminated AT/RT lesion model
                      and immunocompetent humanized mouse models
                      (hCD34+-NSG-SGM3).Delta-24-RGD infected and replicated
                      efficiently in all the cell lines tested. In addition, the
                      virus induced dose-dependent cytotoxicity (IC50 below 1
                      PFU/cell) and the release of immunogenic markers. Invivo, a
                      single intratumoral Delta-24-RGD injection (107 or 108 PFU)
                      significantly increased survival and led to long-term
                      survival in AT/RT and PNET models. Delta-24-RGD hindered the
                      dissemination of AT/RTs and increased survival, leading to
                      $70\%$ of long-term survivors. Of relevance, viral
                      administration to established tumor masses (30 days after
                      engraftment) showed therapeutic benefit. In humanized
                      immunocompetent models, Delta-24-RGD significantly extended
                      the survival of mice bearing AT/RTs or PNETs (ranging from
                      11 to 27 days) and did not display any toxicity associated
                      with inflammation. Immunophenotyping of Delta-24-RGD-treated
                      tumors revealed increased CD8+ T cell
                      infiltration.Delta-24-RGD is a feasible therapeutic option
                      for AT/RTs and CNS-PNETs. This work constitutes the basis
                      for potential translation to the clinical setting.},
      cin          = {B062},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33376098},
      doi          = {10.1158/1078-0432.CCR-20-3313},
      url          = {https://inrepo02.dkfz.de/record/166637},
}