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@ARTICLE{Hammer:126656,
      author       = {K. Hammer$^*$ and A. Kazcorowski$^*$ and L. Liu$^*$ and M.
                      Behr$^*$ and P. Schemmer and I. Herr$^*$ and D.
                      Nettelbeck$^*$},
      title        = {{E}ngineered adenoviruses combine enhanced oncolysis with
                      improved virus production by mesenchymal stromal carrier
                      cells.},
      journal      = {International journal of cancer},
      volume       = {137},
      number       = {4},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-02684},
      pages        = {978 - 990},
      year         = {2015},
      abstract     = {Oncolytic viruses have demonstrated in pre-clinical and
                      clinical studies safety and a unique pleiotropic activity
                      profile of tumor destruction. Yet, their delivery suffers
                      from virus inactivation by blood components and
                      sequestration to healthy tissues. Therefore, mesenchymal
                      stromal cells (MSCs) have been applied as carrier cells for
                      shielded virus delivery to tumors after ex vivo infection
                      with oncolytic viruses. However, infection and particle
                      production by MSCs have remained unsatisfying. Here, we
                      report engineered oncolytic adenoviruses (OAds) for improved
                      virus production and delivery by MSCs. OAds are uniquely
                      amenable to molecular engineering, which has facilitated
                      improved tumor cell destruction. But for MSC-mediated
                      regimens, OAd engineering needs to achieve efficient
                      infection and replication in both MSCs and tumor cells. We
                      show that an Ad5/3 chimeric OAd capsid, containing the
                      adenovirus serotype 3 cell-binding domain, strongly
                      increases the entry into human bone marrow-derived MSCs and
                      into established and primary pancreatic cancer cells.
                      Further, we reveal that OAd with engineered post-entry
                      functions-by deletion of the anti-apoptotic viral gene
                      E1B19K or expression of the death ligand TRAIL--markedly
                      increased virus titers released from MSCs, while MSC
                      migration was not hampered. Finally, these virus
                      modifications, or viral expression of FCU1 for local 5-FC
                      prodrug activation, improved tumor cell killing implementing
                      complementary cytotoxicity profiles in a panel of pancreatic
                      cancer cell cultures. Together, our study establishes
                      post-entry modification of OAd replication for improving
                      virus delivery by carrier cells and suggests a panel of
                      optimized OAds for future clinical development in
                      personalized treatment of pancreatic cancer.},
      cin          = {G403 / F110},
      ddc          = {610},
      cid          = {I:(DE-He78)G403-20160331 / 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:25604186},
      doi          = {10.1002/ijc.29442},
      url          = {https://inrepo02.dkfz.de/record/126656},
}