Combination of B7-H3 vaccination and Id-1 silencing eliminates melanoma in the murine B16 melanoma model in vivo

Traditional therapies of malignant melanoma, such as surgical excision, demonstrate limitations of therapeutic effects in the late-stage melanoma. The emerging therapies, including immune therapy, gene therapy and combination therapy, have exhibited the superiority of the therapeutic effects. Using B16 melanoma model in Kunming mice, we demonstrated that both B7-H3 vaccination and Id-1 silencing highly suppressed the tumor growth and improved the survival rate in B16 melanoma model. Significantly, the combination of B7-H3 vaccination and Id-1 silencing eventually eliminated the tumors, and demonstrated a remarkable survival rate (66.67%) 150 days post tumor implantation. The enhanced cytotoxic activities of the splenic lymphocytes and increased serum IFN-gamma levels from B7-H3 vaccinated mice indicated the tumor suppression might be mediated by the immune response. Consistent with the expressions of Id-1, the expressions of VEGF of Id-1 silencing tumor tissue were significantly reduced. Interestingly, the apoptotic cells in the tumor tissue from the mice received B7-H3 vaccination and Id-1 silencing combination treatment were significantly increased compared to the mice only treated with Id-1 silencing, suggesting the importance of apoptosis in the suppression of tumor growth mediated by Id-1, and also the facilitation of B7-H3 in the process. Taken together, these findings indicate that therapeutic alliance of B7-H3 immunization and Id-1 silencing is a valid approach of the treatment of malignant melanoma. Immune responses, suppression of angiogenesis and induction of apoptosis might be implicated in the process.