Gene therapy of malignant brain tumors: a rat glioma line bearing the herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells

J Neurosci Res. 1992 Nov;33(3):493-503. doi: 10.1002/jnr.490330316.


Tumor cells infected with a retrovirus vector (VIK) containing the herpes simplex virus thymidine kinase (HSV-TK) gene can be selectively killed by treatment with nucleoside analogues, such as ganciclovir. To mediate delivery of the HSV-TK gene to "recipient" tumor cells, "donor" C6 rat glioma cells infected with the VIK vector (C6VIK) were superinfected with wild type Moloney murine leukemia virus (WT Mo-MLV). These modified donor cells (C6VIKWT) produced both wild type retrovirus and the VIK vector. In culture, C6VIKWT cells were 300-fold more sensitive to the toxicity of ganciclovir than were C6VIK cells, suggesting that the presence of wild type retrovirus contributed to the toxicity. Co-culture of C6VIKWT cells with the C6 subline, C6BAG, sensitized the latter to ganciclovir treatment. Nude mice inoculated subcutaneously with a mixture of C6VIKWT and C6BAG cells showed regression of subsequent tumors when treated with ganciclovir. The observations show that tumor cells modified in culture by infection with a retrovirus bearing the HSV-TK gene and wild type retrovirus are not only sensitive to ganciclovir, but can transfer this sensitivity to neighboring "naive" tumor cells in culture and in vivo.

Publication types

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

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Cell Survival / drug effects
  • Female
  • Ganciclovir / pharmacology
  • Genetic Therapy*
  • Glioma / genetics
  • Glioma / therapy*
  • Mice
  • Mice, Nude
  • Moloney murine leukemia virus / enzymology
  • Moloney murine leukemia virus / genetics
  • Rats
  • Retroviridae / enzymology*
  • Retroviridae / genetics
  • Simplexvirus / enzymology
  • Simplexvirus / genetics*
  • Thymidine Kinase / genetics*
  • Tumor Cells, Cultured


  • Thymidine Kinase
  • Ganciclovir