Immunotherapy based on dendritic cells pulsed with CTPFoxM1 fusion protein protects against the development of hepatocellular carcinoma

Abstract

Application of dendritic cells (DCs) pulsed with tumor-associated antigens is considered attractive in immunotherapy for hepatocellular carcinoma (HCC). In order to efficiently prime tumor-associated antigens specific for cytotoxic T lymphocytes (CTLs), it is important that DCs present tumor-associated antigens on MHC class I. MHC class I generally present endogenous antigens expressed in the cytosol. In this study, we developed a new antigen delivery tool based on cross presentation of exogenous antigens in DCs by using cytoplasmic transduction peptide (CTP). CTP protein could transduce FoxM1 tumor antigen into the cytosol of DCs, and CTP-FoxM1 fusion protein could stimulate activation and maturation of DCs. DCs pulsed with CTP-FoxM1 could induce specific CTLs. More importantly, the immunity induced by DCs loaded with CTP-FoxM1 could significantly inhibit tumor growth and metastasis in HCC-bearing mice, which was more potent than that induced by DCs loaded with FoxM1 or CTP, alone. Our results indicate that DCs pulsed with CTP-FoxM1 might be a promising vaccine candidate for HCC therapy and provide new insight into the design of DC-based immunotherapy.