科研之友
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摘要
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Tumor specific cellular and Immoral 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 HBc Delta-5L, using HBc carrier with multiple T cell and B cell sequence insertions. We developed the HBc Delta carrier containing insertions of multiple CTL and T helper (Th) epitopes, which were selected from HCC tumor associated antigens (TAAs) including a fetoprotein (AFP), melanoma antigen gene (MAGE) and telomerase reverse transcriptase (TERT) antigen, and ligands for EGFR and IGFR, designated HBc Delta-5L. LDH release assay and IFN-gamma ELISPOT assay were carried to determine whether HBc Delta-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 HBc Delta-5L were also identified. LDH release assay revealed that PBMC from HCC donor group (n=8) stimulated with HBc Delta-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-gamma from PBMC of HCC donor group in response to HBc Delta-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 HBc Delta-5L recombinant particles using HBc Delta as carrier and suggested that it could be important in design of immunotherapeutic approaches.
