title: Generation of a novel, cyclooxygenase-2-targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy.
abstract: BACKGROUND
  Oncolytic adenoviruses provide a promising alternative for cancer treatment. Recently, adjuvant interferon (IFN)-alfa has shown significant survival benefits for pancreatic cancer, yet was impeded by systemic toxicity. To circumvent these problems adenovirus with high-level targeted IFN-alfa expression can be generated.
  
  
  METHODS
  Conditionally replicative adenoviruses (CRAds) with improved virulence and selectivity for pancreatic cancer were generated. The vectors were tested in vitro, in vivo, and in human pancreatic cancer and normal tissue specimens.
  
  
  RESULTS
  Adenoviral death protein and fiber modifications significantly improved oncolysis. CRAds selectively replicated in vitro, in vivo and showed persistent spread in cancer xenografts. They showed high-level replication in human pancreatic cancer specimens, but not in normal tissues. Improved IFN-CRAd oncolytic efficiency was shown.
  
  
  CONCLUSIONS
  Optimized cyclooxygenase-2 CRAds show highly favorable effects in vitro and in vivo. We report a pancreatic cancer-specific, highly virulent, IFN-expressing CRAd, and we believe that adenovirus-based IFN therapy offers a new treatment opportunity for pancreatic cancer patients.
authors: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Leonard
authors: L
authors: Armstrong
authors: Amanda
authors: A
authors: Arrington
authors: Joohee
authors: J
authors: Han
authors: Tatyana
authors: T
authors: Gavrikova
authors: Eric
authors: E
authors: Brown
authors: Masato
authors: M
authors: Yamamoto
authors: Selwyn M
authors: SM
authors: Vickers
authors: Julia
authors: J
authors: Davydova
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017503:Adenovirus E3 Proteins / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D017503:Adenovirus E3 Proteins; D014408:Biomarkers, Tumor; D016898:Interferon-alpha; C099609:adenovirus death protein, Adenovirus; D051546:Cyclooxygenase 2