Augmented antitumor effects of combination therapy with interleukin-12, cisplatin, and tumor necrosis factor-α in a murine melanoma model

Interleukin-12 (IL-12) has demonstrated antitumor activity in many murine tumor models. However, toxic effects resulting from treatment with IL-12 have been also described. Combining IL-12 with other antineoplastic agents could potentiate its antitumor efficacy and, furthermore, could minimize its toxicity by reducing the doses necessary to achieve the antitumor activity. We examined in a murine melanoma model the efficacy of combination tumor chemo-immunotherapy based on administration of IL-12 cisplatin (CDDP), and tumor necrosis factor-alpha (TNF-alpha). In the current study pairs of: IL-12 + CDDP and IL-12 + TNF-alpha, showed stronger antitumor activity than either agent given alone. Furthermore, combination tumor therapy with IL-12 + CDDP + TNF-alpha was more effective at retarding local tumor growth than either IL-12 + CDDP, IL-12 + TNF-alpha or CDDP + TNF-alpha combination therapies. Our observations indicate that combining of CDDP with IL-12 and IL-12 with TNF-alpha as well as using the triple combination of CDDP, IL-12 and TNF-alpha could be beneficial in tumor therapy.