HSV-1 thymidine kinase gene therapy for colorectal adenocarcinoma-derived peritoneal carcinomatosis

Gene Ther. 1997 Nov;4(11):1189-94. doi: 10.1038/sj.gt.3300520.


Peritoneal carcinomatosis is a common clinical situation which, in most cases, cannot be eradicated by surgery or chemotherapy. The feasibility of an HSV-TK-based suicide gene therapy for peritoneal carcinomatosis induced by DHD/K12 colon carcinoma cells was investigated. DHD/K12 cells stably expressing the tk gene were killed in vitro in the presence of low concentrations of ganciclovir, they exhibited a 'bystander effect' when mixed with TK-negative cells. BD-IX rats injected intraperitoneally, either directly or after surgical peritoneal irritations, with DHD/K12 cells developed peritoneal carcinomatosis within 2 weeks. Ganciclovir treatment of animals injected with DHD/K12-TK cells allowed a significant reduction of the tumor volume as well as a prolonged survival. Of these animals 35-40% showed a long-term disease-free survival after ganciclovir therapy. Residual or relapsing tumors could be explained by a low expression of the transgene as demonstrated by RT-PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality
  • Adenocarcinoma / therapy*
  • Animals
  • Antimetabolites / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / therapy*
  • Combined Modality Therapy
  • Ganciclovir / therapeutic use
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Herpesvirus 1, Human / enzymology
  • Neoplasms, Experimental
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / secondary*
  • Peritoneal Neoplasms / therapy
  • Rats
  • Survival Rate
  • Thymidine Kinase / genetics*
  • Transgenes
  • Tumor Cells, Cultured


  • Antimetabolites
  • Thymidine Kinase
  • Ganciclovir