Overexpression of interleukin‐15 in vivo enhances antitumor activity against mhc class I‐negative and ‐positive malignant melanoma through augmented NK activity and cytotoxic T‐cell response

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Abstract
Interleukin (IL)‐15, a pleiotropic cytokine, is involved in the development and maintenance of NK cells and memory CD8+ T cells. We examined the effects of in vivo overexpression of IL‐15 on protection against 2 types of murine B16 melanoma lines, MHC class I‐negative B16.44 and MHC class I‐positive B16F10 cells, using IL‐15 transgenic (Tg) mice that we have recently constructed. The tumor growth was severely retarded in IL‐15 Tg mice after subcutaneous (s.c.) inoculation with B16.44 or B16F10 cells. IL‐15 Tg mice showed an augmented NK cell activity against B16.44 cells, and in vivo depletion of NK cells by anti‐asialoGM1 Ab treatment abrogated the antitumor activity in IL‐15 Tg mice. On the other hand, IL‐15 Tg mice inoculated with B16F10 cells developed a significant level of CTL response against B16F10 cells, and in vivo depletion of CD8+ T cells by anti‐CD8 MAb treatment abrogated the antitumor activity. Thus, overexpression of IL‐15 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible therapeutic application of IL‐15 for human neoplasms expressing a wide range of MHC class molecules.