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연세대학교 의과대학 Yonsei Medical Journal Yonsei Medical Journal 제58권 제1호
발행연도
2017.1
수록면
43 - 50 (8page)

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Purpose: To identify new immunogenic HLA-A*33;03-restricted epitopes from the human papillomavirus (HPV) 16 E7 proteinfor 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 cytometryand 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 productionfrom peripheral blood mononuclear cells (PBMCs), and CD8+ CTLs sensitized with E749-63 showed higher cytotoxic effect againstSNU1299 cells than did CD8+ CTLs sensitized with other peptides or a negative control group. Thirteen 9- or 10-amino acid overlappingpeptides spanning E749-63, E750-59 (AHYNIVTFCC), and E752-61 (YNIVTFCCKC) induced significantly higher IFN-γ productionand 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 peptidesresult in an antitumor effect against cervical cancer cells. These epitopes could be useful for immune monitoring and immunotherapyfor cervical cancer and HPV 16-related diseases including anal cancer and oropharyngeal cancer.

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