Oncolytic adenoviral therapy in gallbladder carcinoma

Surgery. 2005 May;137(5):527-35. doi: 10.1016/j.surg.2004.12.014.


Background: Oncolytic adenoviral therapy is a promising new approach for cancer treatment. The aim of this study was to improve the conditionally replicative adenoviruses (CRAds) for gallbladder cancer therapy by modifying the fiber-knob region for infectivity enhancement and by incorporating tumor-specific promoters (TSPs) for enhanced specificity.

Methods: For promoter-controlled replication, in vitro efficacy of eight TSPs was investigated in two gallbladder cancer cell lines (NOZ and OCUG-1). Infectivity enhancement was analyzed by two different fiber modifications: Arg-Gly-Asp (RGD) incorporation into the HI loop (RGD modification) and a chimeric construct with a serotype 5 shaft and a serotype 3 knob (5/3 fiber modification). Comparisons were made by infectivity analysis and cytotoxicity assays in vitro, followed by tumor suppressive effects tested in vivo.

Results: Among TSPs, highest potency was exhibited by the cyclooxygenase-2 (COX-2), Midkine, and vascular endothelial growth factor promoters in both cell lines tested. Fiber chimera (Ad5/3Luc1) conferred significant enhancement of Ad infectivity in comparison with unmodified and RGD-modified vectors. COX-2 CRAds demonstrated selective cytocidal effect in gallbladder cancer cells in vitro. COX-2 promoter-based Ad5/3 CRAds showed significantly enhanced tumor-suppressive effect compared with nonreplicative and RGD-modified CRAd vectors in vivo.

Conclusions: The 5/3 fiber-modified, COX-2 promoter-driven CRAds may prove to be a new agent for the treatment of gallbladder carcinoma.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae*
  • Animals
  • Carcinoma / therapy*
  • Cell Line, Tumor
  • Cyclooxygenase 2
  • Female
  • Gallbladder Neoplasms / therapy*
  • Gene Transfer Techniques
  • Genetic Vectors*
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Nude
  • Promoter Regions, Genetic
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • Transcription, Genetic
  • Virus Replication


  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases