Anti-tumor effects of immunotherapeutic peptide on the treatment of hepatocellular carcinoma with HBc carrier

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Tumor specific cellular and humoral immunotherapy may be a viable approach for the treatment of HCC. This study investigated specific inhibitory and cytotoxic effects on hepatocellular carcinoma (HCC) induced by the peptide, designated HBcΔ-5L, using HBc carrier with multiple T cell and B cell sequence insertions. We developed the HBcΔ carrier containing insertions of multiple CTL and T helper (Th) epitopes, which were selected from HCC tumor associated antigens (TAAs) including α fetoprotein (AFP), melanoma antigen gene (MAGE) and telomerase reverse transcriptase (TERT) antigen, and ligands for EGFR and IGFR, designated HBcΔ-5L. LDH release assay and IFN-γ ELISPOT assay were carried to determine whether HBcΔ-5L could induce specific cytotoxicity in peripheral blood mononuclear cells (PBMC) of HCC donors. The levels of antibodies and inhibitory effects of sera of immunized mice against HBcΔ-5L were also identified. LDH release assay revealed that PBMC from HCC donor group (n=8) stimulated with HBcΔ-5L could specifically kill target tumor cells and specific lysis was 62.7% (E:T=60:1). ELISPOT assay showed a significant increase in secretion of IFN-γ from PBMC of HCC donor group in response to HBcΔ-5L. Further, high specific antibody titers were elicited in immunized mice and revealed 42% inhibition of cell growth. These results indicated that inhibitory and cytotoxic effects could be efficiently induced by HBcΔ-5L recombinant particles using HBcΔ as carrier and suggested that it could be important in design of immunotherapeutic approaches.