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Identificaiton of Novel Immunogenic Human Papillomavirus Type 16 E7-Specific Epitopes Restricted to HLA-A*33;03 for Cervical Cancer Immunotherapy.

 Sunghoon Kim  ;  Hye Won Chung  ;  Hoon Young Kong  ;  Jong-Baeck Lim 
 Yonsei Medical Journal, Vol.58(1) : 43-50, 2017 
Journal Title
 Yonsei Medical Journal 
Issue Date
Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Epitopes/immunology* ; Epitopes/therapeutic use ; Female ; HLA-A Antigens* ; Human papillomavirus 16/immunology* ; Humans ; Immunotherapy* ; Interferon-gamma/analysis ; Interferon-gamma/biosynthesis* ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; Uterine Cervical Neoplasms/therapy*
HLA-A*33 ; 03 ; HPV 16 E7 ; cervical cancer ; epitopes ; immunotherapy
Purpose : To identify new immunogenic HLA-A*33;03-restricted epitopes from the human papillomavirus (HPV) 16 E7 protein for immunotherapy against cervical cancer. Materials and Methods : We synthesized fourteen overlapping 15-amino acid peptides and measured intracellular interferon-γ (IFN-γ) production in PBMC and CD8+ cytotoxic T lymphocytes (CTLs) after sensitization with these peptides using flow cytometry and ELISpot assay. The immunogenicity of epitopes was verified using a 51Cr release assay with SNU1299 cells. Results : Among the fourteen 15-amino acid peptides, E749-63 (RAHYNIVTFCCKCDS) demonstrated the highest IFN-γ production from peripheral blood mononuclear cells (PBMCs), and CD8+ CTLs sensitized with E749-63 showed higher cytotoxic effect against SNU1299 cells than did CD8+ CTLs sensitized with other peptides or a negative control group. Thirteen 9- or 10-amino acid overlapping peptides spanning E749-63, E750-59 (AHYNIVTFCC), and E752-61 (YNIVTFCCKC) induced significantly higher IFN-γ production and cytotoxic effects against SNU1299 cells than the other peptides and negative controls, and the cytotoxicity of E750-59- and E752-61-sensitized PBMCs was induced via the cytolytic effect of CD8+ CTLs. Conclusion : We identified E750-59 and E752-61 as novel HPV 16 E7 epitopes for HLA-A*33;03. CD8+ CTL sensitized with these peptides result in an antitumor effect against cervical cancer cells. These epitopes could be useful for immune monitoring and immunotherapy for cervical cancer and HPV 16-related diseases including anal cancer and oropharyngeal cancer.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
공훈영(Kong, Hoon Young)
김성훈(Kim, Sung Hoon) ORCID logo https://orcid.org/0000-0002-1645-7473
임종백(Lim, Jong Baeck) ORCID logo https://orcid.org/0000-0003-0419-0422
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