A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor

Hum Gene Ther. 1997 Oct 10;8(15):1807-14. doi: 10.1089/hum.1997.8.15-1807.


Antitumor gene therapy using herpes simplex type 1 thymidine kinase (TKh) and ganciclovir (GCV) treatment has revealed an important intratumoral bystander effect. A whole tumor can be eliminated when only a fraction of its tumor cells express TKh. We now report that the bystander effect not only acts within a tumor, but also between distant tumors. One TKh+ tumor was generated simultaneously with one or multiple TKh- tumors in different rat liver lobes such that there was no contact between the resulting tumors. Both the TKh+ and the TKh- tumors regressed after GCV treatment and showed infiltration with macrophages and T lymphocytes. This distant bystander effect, which is likely immune mediated, should be of major importance for gene therapy of disseminated tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Carcinoma, Hepatocellular / therapy*
  • Cell Transformation, Viral
  • Colonic Neoplasms / secondary
  • Colonic Neoplasms / therapy*
  • Ganciclovir / therapeutic use*
  • Genetic Therapy*
  • Genetic Vectors
  • Herpesvirus 1, Human / enzymology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Mice
  • Rats
  • Remission Induction
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / therapeutic use
  • Tumor Cells, Cultured


  • Thymidine Kinase
  • Ganciclovir