Adoptive cell transfer enhances antitumor response generated by Cytomegalovirus-based vaccine

Methods for generating long-lived T cell responses to tumor antigen have been highly sought for potential therapy against many cancers. Our group has recently developed a novel vaccine against melanoma using recombinant Mouse Cytomegalovirus (MCMV) expressing a modified tumor antigen which generated life-long CD8+ T cell responses to the melanoma antigen, gp100. While this vaccine delays tumor growth in a mouse model of B16 metastatic melanoma, mice eventually succumb to the disease. Adoptive cell therapy has shown clinical efficacy in some patients with melanoma; however, it requires in vitro activation of large numbers of T cells to be effective. We hypothesized that combining these therapies would result in more effective tumor rejection by 1) increasing precursor frequency of tumor specific T cells, thus inducing a more robust T cell response following vaccination and 2) promoting life-long persistence of transferred cells following transfer. To test this, C57BL/6 mice received 105 CD8+ T cells expressing a transgenic T cell receptor recognizing gp100 (PMEL) followed by vaccination. Five days after transfer, PMEL cells constituted up to 20% of all CD8+ T cells in peripheral blood following MCMV vaccination in contrast to 7.5% following vaccination with another viral vaccine, Vesicular Stomatitis Virus. Our results also show that adoptive transfer and MCMV vaccination delays B16 tumor growth and improves survival in a solid tumor model. In summary, this study tests a novel method for stimulating adoptively transferred antitumor T cells, while avoiding the need for long-term in vitroculture of cells. Future work will also examine if immune checkpoint inhibitors or costimulatory agonists further improve this therapy.