Folate-modified chitosan nanoparticles coating IP-10 promote pMAGE-A1278-286 specific CTL responses to liver cancer (VAC11P.1011)

Abstract

Abstract Adoptive therapy using tumor antigen-specific cytotoxic T lymphocytes (CTLs) is a promising approach for the treatment of human cancers. However, tumor antigen-specific CTLs are difficult to reach tumor tissues because of immune suppressions in cancer patients. Interferon-inducible protein-10 (IP-10), a powerful chemokines, effectively attracts CTLs to tumor tissues and improves the anti-tumor activity of CTLs. Increasing the expression of IP-10 in tumor tissues can efficiently promote the efficacy of adoptive therapy. In this study, we developed folate-modified chitosan nanoparticles coating the human IP-10 gene (FA-CS-hIP-10), that specifically bound to the folate receptors on hepatoma cells and promote the expression of IP-10 to improve the activity of pMAGE-A1278-286 specific CTLs. Combination of FA-CS-hIP-10 and pMAGE-A1278-286 specific CD8+ CTLs efficiently increased the secretion of IFN-γ, inhibited the growth of tumor and extend the survival of nude mice subcutaneously transplanted human liver cancer. Our results demonstrated that the mechanism of this novel adoptive therapy involved in the inhibition of angiogenesis, inhibition of proliferation, and promotion of apoptosis of tumor cells. Our study provided a potentially novel approach for the treatment of human liver cancers by improving the activity of tumor antigen-specific CTLs.