Cytomegalovirus-based cancer vaccines expressing TRP2 induce potent antitumor effect against melanoma in mice (156.20)

Abstract

Abstract Cytomegalovirus (CMV) induces strong and long-lasting immune responses, which make it an attractive candidate for a cancer vaccine vector. In this study, we tested whether a tumor antigen expressed in CMV can induce an anti-tumor effect. We expressed the melanoma tumor antigen, tyrosinase-related protein 2 (TRP2), in murine cytomegalovirus (MCMV). A single prophylactic dose of MCMV-TRP2 induced complete rejection of B16 melanoma cells. In a therapeutic setting, MCMV-TRP2 significantly inhibited the growth of melanoma. In addition, the growth of B16 cells inoculated five months after a single vaccination with MCMV-TRP2 was still inhibited, which indicates the vaccine induced a long-term protection. MCMV-TRP2 induced the production of both TRP2-specific CD8 T cells and antibodies. Depletion of CD4 and CD8 T cells did not compromise the antitumor effect, but MCMV-TRP2-vaccinated B cell deficient (µMT) mice did not reject B16 cells. This indicated that antibody rather than T cells was the main mediator of the antitumor effect induced by MCMV-TRP2. We also made a spread-deficient MCMV-TRP2 vaccine, which showed a similar antitumor effect. In conclusion, our study indicates that TRP2 expressed in MCMV induces a strong and long-lasting anti-melanoma effect through an antibody dependent mechanism. Our findings demonstrated for the first time that CMV is a promising vector for cancer vaccines.