The presence of
tumor-infiltrating CD8(+) T cells is associated with
tumor regression and better prognosis. Cytomegalovirus (CMV)
infection elicits a robust and long-lasting CD8(+) T-cell response, which makes CMV a potentially promising
vaccine vector against
cancer. In the current study, we used recombinant murine CMV (MCMV) strains as prophylactic and therapeutic
vaccines in an aggressive B16 lung metastatic
melanoma model. Immunization with MCMV-expressing
ovalbumin (OVA) induced a potent OVA-specific CD8(+) T-cell response and was effective in protecting mice from OVA-expressing
B16 melanoma in an
antigen-dependent manner. We engineered MCMV to express a modified
B16 melanoma antigen gp100 (MCMV-gp100KGP). Immunization with MCMV-gp100KGP was highly effective in overcoming immune tolerance to
self-antigen and induced a strong, long-lasting gp100-specific CD8(+) T-cell response even in the presence of preexisting anti-CMV immunity. Furthermore, both prophylactic and therapeutic vaccinations of mice with MCMV-gp100KGP effectively protected mice from highly aggressive lung B16-F10
melanoma, and the protection was mediated by gp100-specific CD8(+) T cells. We showed that MCMV is a superior
vaccine vector compared with a commonly used
vesicular stomatitis virus vector. Collectively, our studies demonstrate that CMV is a promising
vaccine vector to prevent and treat
tumors.