Interleukin 15 augments antitumor activity of cytokine gene-modified melanoma cell vaccines in a murine model

Many studies have demonstrated that interleukin 15 (IL-15) is a cytokine with strong antitumor properties and have suggested its potential use in tumor immunotherapy. IL-15 exerts its effect on innate and acquired immunity with the most prominent action in NK cells and CD8(+) memory T cells. Therefore, many authors have proposed that IL-15 could be a good candidate for augmenting the efficacy of vaccination strategies. In our experiments, in a model of B78-H1 murine transplantable melanoma, tumor-bearing mice were treated with different cytokine-gene modified tumor cell vaccines (producing TNF-alpha, GM-CSF, IL-12 or IL-6/sIL-6R) followed by a series of IL-15 injections. In order to investigate the infiltration of treated tumors by leukocytes, immunohistochemical staining was performed. In every case, the combined therapy was superior to the treatment with either a vaccine or IL-15 alone. Tumors treated with the combination of B78-H1 melanoma cells secreting IL-12 (B78/IL-12 vaccine) and IL-15 were heavily infiltrated by granulocytes. IL-15, either alone or in combination with the B78/IL-12 vaccine, influenced infiltration of tumors with CD3(+) lymphocytes, CD4(+)and CD8(+). To our knowledge, this is the first report that shows the universal genetically-modified tumor cell vaccine-augmenting properties of IL-15. The cytokine can be useful as an adjuvant in cancer gene therapy in humans.