Interleukin-15 (IL-15) has gained significant attention as an adjuvant in cancer vaccine strategies, but it has a complex number of immune stimulatory activities and the basis for its contribution to effective vaccine responses is incompletely understood. IL-15 is presented in trans to T, B, and NK cells by presentation from its receptor, IL-15Rα, which is expressed on dendritic cells (DC) and monocytes. In this study, we examined the ability of IL-15 to augment a DC vaccine directed against the HER2/Neu oncoprotein, using adenoviral-mediated transfer of the IL-15, IL-15R, and Neu genes to DCs used in the vaccine. Transgenic BALB-neuT mice treated with the Neu.DC vaccine during late-stage tumor developmen... More
Interleukin-15 (IL-15) has gained significant attention as an adjuvant in cancer vaccine strategies, but it has a complex number of immune stimulatory activities and the basis for its contribution to effective vaccine responses is incompletely understood. IL-15 is presented in trans to T, B, and NK cells by presentation from its receptor, IL-15Rα, which is expressed on dendritic cells (DC) and monocytes. In this study, we examined the ability of IL-15 to augment a DC vaccine directed against the HER2/Neu oncoprotein, using adenoviral-mediated transfer of the IL-15, IL-15R, and Neu genes to DCs used in the vaccine. Transgenic BALB-neuT mice treated with the Neu.DC vaccine during late-stage tumor development were protected from arising mammary carcinomas, with 70% of the Neu.DC-vaccinated animals tumor-free at 30 weeks. Combining the Neu, IL-15, and IL-15Rα genes increased the anti-Neu antibody response compared with mice lacking one of these components. Antitumor effects were found to be antibody mediated and to involve modulation of Neu expression and signaling. Depleting CD4+ T cells did not abrogate the antitumor properties of the complete vaccine, nor did it inhibit the induction of anti-Neu antibodies. Our findings show that augmenting IL-15 signaling can increase the anticancer efficacy of a DC vaccine by promoting antibody production, apparently bypassing or overcoming impairments in CD4+ T-helper function. Cancer Res; 70(3); 1072 -81
