GANCICLOVIR CHEMOABLATION OF HERPES THYMIDINE KINASE SUICIDE GENE-MODIFIED TUMORS PRODUCES TUMOR NECROSIS AND INDUCES SYSTEMIC IMMUNE-RESPONSES

The goal of this work was to identify potential host immune responses to thymidine kinase (TK) suicide gene-modified tumors undergoing chemo ablation induced by the prodrug ganciclovir (GCV), The aims were to me asure the efficacy and specificity of immunity induced against unmodif ied tumor, to identify qualitative or quantitative changes in the host response to TK+ tumors undergoing chemoablation that may contribute t o the induction of antitumor immunity, and to compare critically the i nduction of immunity by chemoablation of TK-modified tumors with that of other methods of immunization in this tumor model and in response t o other well-defined model antigens, Animals treated with TK+ tumors a nd GCV developed specific resistance to rechallenge with unmodified tu mor. GCV induced significant tumor necrosis, which was associated with a pronounced host cell infiltrate composed of polymorphonuclear cells , both CD4(+) and CD8(+) T lymphocytes, and increased intratumoral IL- 12. Cyclophosphamide-treated mice exhibited no such host response desp ite the induction of tumor necrosis, CTL responses to defined antigens in TK+ cells were greater in animals treated with prodrug than were t hose in animals not treated with prodrug but harboring live TK+ cells. Similar degrees of immunity were produced by immunization with irradi ated cells.