Anti‐tumor immunity induced by tumor cells express a membrane‐bound form of IL‐2 and SDF‐1

Abstract

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.

Key words:

• membrane‐bound form of IL‐2
• SDF‐1
• tumorigenicity
• systemic anti‐tumor immunity

Notes

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Additional information

Notes on contributors

Young Sang Kim

*