Immunotherapy of mice with an irradiated melanoma vaccine coupled with interleukin-12

Interleukin (IL)-12 can activate cytotoxic lymphocytes, stimulate natural k iller cell activity, induce the production of INF-gamma and inhibit the dev elopment of various experimental tumors. We previously demonstrated that im munotherapy of melanoma bearing mice with an irradiated melanoma vaccine (I MV) coupled with IL-2 or GM-CSF had beneficial effects against primary mela noma growth and against subsequent spontaneous metastasis. We also had foun d that treatment of melanoma bearing mice with IL-12 (300 ng/day) for 4 wee ks inhibited the development of primary melanoma tumors in 40% of mice. The purpose of this study was to investigate the efficacy of combined therapy of experimental melanoma with an IMV prepared from B16F10 melanoma cells co upled with IL-12 treatment. C57BL/6 mice were challenged subcutaneously in the tail with B16F10 melanoma cells and by the 45th day, more than 50% of t he mice had developed visible primary melanoma tumors at the injection site . Subsequent immunotherapy of mice with IMV, when coupled with IL-12, provi ded partial inhibition of primary melanoma tumor growth. Optimal results ag ainst primary tumor growth were observed when IMV therapy was coupled with IL-12 at a dose of 50 ng/day. Combination of IMV with IL-12 at a dose of 10 0 ng/day significantly reduced melanoma metastasis to the lungs compared wi th control mice, and an improvement in mean survival time was observed in m ice treated with a combination of IMV with IL-12 (300 ng/day).