Folate-Modified Chitosan Nanoparticles Coated Interferon-Inducible Protein-10 Gene Enhance Cytotoxic T Lymphocytes' Responses to Hepatocellular Carcinoma.

Abstract

Adoptive therapy using tumor antigen-specific cytotoxic T lymphocytes (CTLs) is a promising approach for treatment of human cancers. Due to immune suppression in cancer patients, it is difficult for tumor antigen-specific CTLs to arrive at tumor tissues. Interferon-inducible protein-10 (IP-10) is a powerful chemokine that effectively attracts CTLs to tumor tissues and improves their anti-tumor activity. Increase over expression of IP-10 in tumor tissues can efficiently promote efficacy of adoptive therapy. Folate-modified chitosan nanoparticles coating the human IP-10 gene (FA-CS-hIP-10) were therefore developed in this study. The FA-CS-hIP-10 nanoparticles were specifically bound to folate receptors on hepatoma cells and promoted the expression of IP-10, to improve the activity of pMAGE-A1(278-286) specific CTLs. Combination of the FA-CS-hIP-10 and pMAGE-A1(278-286) specific CD8+ CTLs efficiently increased secretion of IFN-γ, inhibited tumor growth and extended survival of nude mice with subcutaneously transplanted human hepatocellular carcinoma. Our results demonstrated that the mechanism behind this novel therapeutic approach involved inhibition of angiogenesis and proliferation, and also promoted apoptosis of tumor cells. Our study provides a potentially novel approach for treatment of human hepatocellular carcinoma by improving the activity of tumor antigen-specific CTLs.