Vaccination with Tumor Cells Expressing IL-15 and IL-15Rα Inhibit Murine Breast and Prostate Cancer

A number of antitumor vaccines have shown recent promise up-regulating immune responses against tumor antigens and improving patient survival. In this study we examine the effectiveness of vaccination using IL-15 expressing tumor cells and examined their ability to up-regulate immune responses to tumor antigens. We demonstrated that the co-expression of IL-15 with its receptor, IL-15Rα, increased the cell-surface expression and secretion of IL-15. We show that a gene transfer approach using recombinant adenovirus to express IL-15 and IL-15Rα in murine TRAMP-C2 prostate or TS/A breast tumors induced antitumor immune responses. From this we developed a vaccine platform, consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells co-expressing IL-15 and IL-15Rα that inhibited tumor formation when mice were challenged with tumor. Inhibition of tumor growth led to improved survival when compared to animals receiving cells expressing IL-15 alone or unmodified tumor cells. Animals vaccinated with tumor cells co-expressing IL-15 and IL-15Rα showed greater tumor infiltration with CD8+ T and NK cells, as well as increased antitumor CD8+ T-cell responses. Vaccination with IL-15/IL-15Rα-modified TS/A breast cancer cells provided a survival advantage to mice challenged with unrelated murine TUBO breast cancer cells indicating the potential for allogeneic IL-15/IL-15Rα expressing vaccines.