PRODRUG-ACTIVATED GENE-THERAPY - INVOLVEMENT OF AN IMMUNOLOGICAL COMPONENT IN THE BYSTANDER EFFECT

The integration and expression of the herpes simplex virus type 1 thym idine kinase (HSV1-TK) gene in localized tumors results in tumor regre ssion after the administration of the specific nucleoside analogue gan ciclovir (GCV). Although only 10% to 20% of the tumor cells lake up th e HSV1-TK gene, the neighboring cells also die, a phenomenon termed th e ''bystander effect.'' In the present study, coinjection of the MC26 mouse colon carcinoma cell line and the HSV1-TK expressing retroviral packaging cell line followed after 7 days by the intraperitoneal admin istration of GCV resulted in almost total tumor regression in the immu nocompetent BALB/c mice but not in immunocompromised athymic BALB/c mi ce. This suggested a strong cell-mediated immune component to the byst ander effect.