Effective tumor immunity to melanoma mediated by B16F10 cancer stem cell vaccine

摘要

Abstract Although tumor vaccines have been considered a promising immunotherapy approach, therapeutic tumor vaccines are mostly disappointing in the clinic due to vaccine weak immunogenicity. Cancer stem cells (CSCs) may broaden the antigenic breadth and effectively induce the immune responses against autologous cancer cells. Here we report on the development of the B16F10 CD133 + CD44 + CSCs (B16F10 CSCs) vaccine to induce tumor immunity to melanoma in mice. Efficacy of against melanoma was evaluated by analysis of tumor growth and mouse survival. Immunogenicity was assessed by ELISA and flow cytometric assays, including serum cytokines, cytotoxic activity of NK cells and splenocytes in the immunized mice. The results showed that the B16F10 CSC vaccine resulted in tumor shrinkage and mouse lifespan extension. The cytotoxic activity and IFN-γ level were significantly increased in mice immunized with B16F10 CSC vaccine compared with the mice immunized with control vaccines. Additionally, New York esophageal squamous cell carcinoma-1, an efficient tumor associated antigen over-expressed by B16F10 CSCs, was markedly reduced in expression in melanoma tissue, suggesting decrease of CSC subpopulation due to B16F10 CSC vaccination. Collectively, the findings may represent a new powerful approach for treatment of melanoma by B16F10 CSC vaccination. Highlights ? B16F10 CD133 + CD44 + cells isolated from B16F10 cell line act as B16F10 CSCs. ? Cancer testis antigen NY-ESO-1 related with immunogenicity overexpressed by B16F10 CSCs. ? Splenocytes in B16F10 CSCs vaccinated mice have robust cytotoxicity in vitro . ? CSC vaccine results in tumor shrinkage and extending tumor-bearing mouse survival. ? CSC vaccine reduces NY-ESO-1 expression in tumor, suggesting decrease of CSC subset.