HSV-1 THYMIDINE KINASE GENE-THERAPY FOR COLORECTAL ADENOCARCINOMA-DERIVED PERITONEAL CARCINOMATOSIS

Peritoneal carcinomatosis is a common clinical situation which, in mos t cases, cannot be eradicated by surgery or chemotherapy. The feasibil ity of an HSV-TK-based suicide gene therapy for peritoneal carcinomato sis induced by DHD/K12 colon carcinoma cells was investigated. DHD/K12 cells stably expressing the tk gene were killed in vitro in the prese nce of low concentrations of ganciclovir, they exhibited a 'bystander effect' when mixed with TK-negative cells. BD-IX rats injected intrape ritoneally, 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 allow ed a significant reduction of the tumor volume as well as a prolonged survival. Of these animals 35-40% showed a long-term disease-free surv ival after ganciclovir therapy. Residual or relapsing tumors could be explained by a low expression of the transgene as demonstrated by RT-P CR.