Identification of new cytotoxic T-lymphocyte epitopes from cancer testis antigen HCA587.
The cancer testis (CT) antigen HCA587 is highly expressed in human hepatocellular carcinoma (HCC) and induces specific T-cell responses in a significant proportion of HCC patients. To explore its potential in cancer immunotherapy, a reverse immunology approach was adopted to identify HCA587-derived HLA-A( *)0201-restricted epitopes. Multiple peptides with a top ranking in various prediction programs were thus synthesized and three of them-p248-256, p140-149 and p144-152-were found to bind to HLA-A(*)0201 molecules with a high affinity and effectively induced a recall response of CD8+ T cells, which were either primed in vitro with the HCA587 antigen or directly isolated from HCC patients bearing HCA587+ tumors. Notably, these peptide-specific CD8+ T cells exhibited potent cytotoxic activity over HCA587+ tumor cells. Taken together, the present study has identified three new HLA-A(*)0201-restricted cytotoxic T cell epitopes in the CT antigen HCA587, which may serve as targets for peptide-based immunotherapy for HCC patients.
Xing
Qiao
Q
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, PR China.
Pang
Xue-Wen
XW
Peng
Ji-Run
JR
Yin
Yan-Hui
YH
Li
Yan
Y
Yu
Xin
X
Zhou
Shu-Pei
SP
Zhang
Yu
Y
Chen
Wei-Feng
WF
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D015234:HLA-A Antigens / Q000032:analysis* / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000276:immunology* / Q000628:therapy; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C405429:MAGEC2 protein, human; D009363:Neoplasm Proteins; D010455:Peptides