Potentiated antitumor effects of interleukin 12 and matrix metalloproteinase inhibitor batimastat against B16F10 melanoma in mice

The application of antiangiogenic agents in cancer therapy has been studied extensively. Combination of agents with antiangiogenic properties could po ssibly enhance antitumor effects. Interleukin 12 is a cytokine with potent antitumor activity mediated also via antiangiogenic mechanisms. These effec ts are attributed to IFN-gamma production stimulated by IL-12. Since IFN-ga mma has been reported to augment antitumor effects when combined with one o f the metalloproteinase inhibitors - batimastat (BB-94), we have examined a combined treatment with IL-12 and BB-94 in a murine melanoma model. The ad ministration of both agents showed potentiated antitumor activity. Furtherm ore, we have shown in a tumor-induced angiogenesis model that the combined application of IL-12 and batimastat inhibits the formation of new blood ves sels to a greater extent than either agent alone. Our observations show tha t antiangiogenic effects are at least partly responsible for the enhanced a ntitumor effects of the combined treatment with IL-12 and BB-94.