Identification of two naturally presented MAGE antigenic peptides from a patient with hepatocellular carcinoma by mass spectrometry.
In the absence of efficient systemic chemotherapy, immunotherapy is considered a hopeful treatment for controlling recurrence of hepatocellular carcinoma (HCC). The identification of proper antigenic peptides presented by MHC class I molecules is a critical step for the development of therapeutic vaccines against tumors. Currently, the "reverse immunology" approach is the most commonly used technique in the identification of the tumor-associated T cell epitopes. However, it is based on T cell dependent approach and cannot fully reflect the actual presentation of epitope in tumor in vivo. In the present study, we managed to identify the naturally presented MAGE epitopes of HCC directly by epitope prediction, HPLC differential analysis and MS detection. We successfully detected a naturally processed peptide FLWGPRALV (MAGE-3(271-279), HLA-A2-restricted) with an estimated number of 38-39 copies/cell in HCC. To our knowledge, this is the first evidence that the naturally processed MAGE-3(271-279) can be isolated and identified from the tumor tissue of HCC patient. Furthermore, specific CD8(+) T cell responses to this epitope were also found after tumor relapse by IFN-gamma release Cytospot and tetramer assay indicating that MAGE-3(271-279) was indeed presented by HCC cells in vivo. In addition, another new antigen peptide was found, which may be derived from MAGE-1. Our findings demonstrate the potential of the direct approach for identification of tumor-associated epitopes. This approach may become a useful tool for the development of vaccine against cancer in the future.
Zhou
Mai
M
Department of Hepatobiliary Surgery, Peking University People Hospital, Beijing 100044, China.
Peng
Ji-Run
JR
Zhang
Hua-Gang
HG
Wang
Hong-Xia
HX
Zhong
Zhao-Hui
ZH
Pan
Xiu-Ying
XY
Chen
Wei-Feng
WF
Leng
Xi-Sheng
XS
D000368:Aged; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry; D058950:Melanoma-Specific Antigens; D009097:Multienzyme Complexes / Q000235:genetics; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; D000939:Epitopes; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex