In vivo and in vitro glioma cell killing induced by an adenovirus expressing both cytosine deaminase and thymidine kinase and its association with interferon-alpha

J Neuropathol Exp Neurol. 1999 Aug;58(8):847-58. doi: 10.1097/00005072-199908000-00007.


An adenovirus, AdCDTK, expressing both bacterial cytosine deaminase (CD) and herpes simplex virus thymidine kinase (HSVTK) was constructed and introduced into glioma cells. AdCDTK selectively rendered glioma cells sensitive to both 5-fluorocytosine (5-FCyt) and ganciclovir (GCV) (termed AdCDTK/5-FCyt-GCV). AdCDTK/5-FCyt-GCV not only potently mediated apoptosis and the arrest of glioma cell growth in vitro, but also significantly increased the survival time of glioma-bearing rats as compared with controls. The 90-day survival time was observed in 50% of rats. Interferon-alpha (IFN-alpha) further enhanced the tumor cell killing of AdCDTK/5-FCyt-GCV. In the group of AdCDTK/5-FCyt-GCV/IFN-alpha, the average survival time was significantly increased, and the average tumor size was smaller than that in the group of AdCDTK/5-FCyt-GCV. Ninety-day survival increased from 50% in the group of AdCDTK/5-FCyt-GCV to 75% in the group of AdCDTK/5-FCyt-GCV/IFN-alpha. Complete tumor regression was observed in 50% of rats in the group of AdCDTK/5-FCyt-GCV/IFN-alpha. The data indicate that AdCDTK/5-FCyt-GCV induces glioma cell killing greater than that induced by either CD/5-FCyt or HSVTK/GCV alone. IFN-alpha synergistically enhances this effect by increasing apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / enzymology
  • Adenoviridae / genetics*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Brain / pathology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Survival / drug effects
  • Cytosine Deaminase
  • DNA, Neoplasm / biosynthesis
  • Flucytosine / metabolism
  • Flucytosine / pharmacology
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Glioma / pathology*
  • Glioma / therapy
  • Glioma / virology
  • Interferon-alpha / pharmacology*
  • Male
  • Neoplasm Transplantation
  • Nucleoside Deaminases / biosynthesis*
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Simplexvirus / enzymology
  • Thymidine Kinase / biosynthesis*
  • Transduction, Genetic
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • DNA, Neoplasm
  • Interferon-alpha
  • RNA, Messenger
  • Flucytosine
  • Thymidine Kinase
  • Nucleoside Deaminases
  • Cytosine Deaminase