Anti-tumor Immunity Induced by Tumor Cells Expressing a Membrane-bound Form of IL-2 and SDF-1

The eventual goal of tumor immunotherapy is to develop a vaccine inducing a specific anti-tumor immunity. Cytokine gene therapy is an effective way at least in animal models, but limited efficacy and various side effects obstruct clinical applications. In this study, we developed a tumor vaccine expressing a membrane-bound form of IL-2(mbIL-2) and SDF-1 in B16F10 melanoma cells. The tumor clones expressing mbIL-2 showed reduced tumorigenicity, and additional expression of SDF-1 to mbIL-2 expressing tumor cells caused more severe reduction in tumorigenicity. However, expression of the SDF-1 alone did not affect on the tumorigenicity, probably because of limited production of SDF-1 in the SDF-1 transfected clones. When the mice once rejected mbIL-2/SDF-1 expressing tumor clone were re-challenged with wild type B16F10 tumor cells, all of the mice survived. This result suggests that mbIL-2/SDF-1 tumor clone is effective in inducing systemic anti-tumor immunity against wild type B16 melanoma. Furthermore, culture supernatant of tumor clones expressing SDF-1 induced lymphocyte migration in vitro. These results, all together, suggest that expression of mbIL-2 and SDF-1 in tumor cells enhances anti-tumor immune responses through different roles; the secreted SDF-1 may function as a chemoattractant to recruit immune cells to tumor vaccine injection site, and the mbIL-2 on tumor cells may provide costimulatory signal for CTL activation in physical contacts.