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@ARTICLE{FernndezUlibarri:126505,
      author       = {I. Fernández-Ulibarri$^*$ and K. Hammer$^*$ and M.
                      Arndt$^*$ and J. K. Kaufmann$^*$ and D. Dorer$^*$ and S.
                      Engelhardt$^*$ and R. E. Kontermann and J. Hess$^*$ and H.
                      Allgayer$^*$ and J. Krauss$^*$ and D. Nettelbeck$^*$},
      title        = {{G}enetic delivery of an immuno{RN}ase by an oncolytic
                      adenovirus enhances anticancer activity.},
      journal      = {International journal of cancer},
      volume       = {136},
      number       = {9},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-02533},
      pages        = {2228 - 2240},
      year         = {2015},
      abstract     = {Antibody therapy of solid cancers is well established, but
                      suffers from unsatisfactory tumor penetration of large
                      immunoglobulins or from low serum retention of antibody
                      fragments. Oncolytic viruses are in advanced clinical
                      development showing excellent safety, but suboptimal potency
                      due to limited virus spread within tumors. Here, by
                      developing an immunoRNase-encoding oncolytic adenovirus, we
                      combine viral oncolysis with intratumoral genetic delivery
                      of a small antibody-fusion protein for targeted bystander
                      killing of tumor cells (viro-antibody therapy).
                      Specifically, we explore genetic delivery of a small
                      immunoRNase consisting of an EGFR-binding scFv antibody
                      fragment fused to the RNase Onconase (ONC(EGFR)) that
                      induces tumor cell death by RNA degradation after cellular
                      internalization. Onconase is a frog RNase that combines lack
                      of immunogenicity and excellent safety in patients with high
                      tumor killing potency due to its resistance to the human
                      cytosolic RNase inhibitor. We show that ONC(EGFR) expression
                      by oncolytic adenoviruses is feasible with an optimized,
                      replication-dependent gene expression strategy.
                      Virus-encoded ONC(EGFR) induces potent and EGFR-dependent
                      bystander killing of tumor cells. Importantly, the
                      ONC(EGFR)-encoding oncolytic adenovirus showed dramatically
                      increased cytotoxicity specifically to EGFR-positive tumor
                      cells in vitro and significantly enhanced therapeutic
                      activity in a mouse xenograft tumor model. The latter
                      demonstrates that ONC(EGFR) is expressed at levels
                      sufficient to trigger tumor cell killing in vivo. The
                      established ONC(EGFR)-encoding oncolytic adenovirus
                      represents a novel agent for treatment of EGFR-positive
                      tumors. This viro-antibody therapy platform can be further
                      developed for targeted/personalized cancer therapy by
                      exploiting antibody diversity to target further established
                      or emerging tumor markers or combinations thereof.},
      keywords     = {Antibodies, Viral (NLM Chemicals) / Antineoplastic Agents
                      (NLM Chemicals) / RNA (NLM Chemicals) / EGFR protein, human
                      (NLM Chemicals) / Receptor, Epidermal Growth Factor (NLM
                      Chemicals) / Ribonucleases (NLM Chemicals)},
      cin          = {F110 / D120 / G405 / G360},
      ddc          = {610},
      cid          = {I:(DE-He78)F110-20160331 / I:(DE-He78)D120-20160331 /
                      I:(DE-He78)G405-20160331 / I:(DE-He78)G360-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25303768},
      doi          = {10.1002/ijc.29258},
      url          = {https://inrepo02.dkfz.de/record/126505},
}