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 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 alpha 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.
Kong
Jing
J
College of Biological Science and Technology, China Pharmaceutical University, Nanjing 210002, P.R. China.
Diao
Zhenyu
Z
Deng
Xiaozhao
X
Zhong
Hui
H
Yao
Wenjuan
W
Hu
Xuefang
X
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D006509:Hepatitis B / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000276:immunology / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D010446:Peptide Fragments; D000509:alpha-Fetoproteins; D007371:Interferon-gamma; C509186:TERT protein, human; D019098:Telomerase