Identificaiton of Novel Immunogenic Human Papillomavirus Type 16 E7-Specific Epitopes Restricted to HLA-A*33;03 for Cervical Cancer Immunotherapy.
- Author:
Sunghoon KIM
1
;
Hye Won CHUNG
;
Hoon Young KONG
;
Jong Baeck LIM
Author Information
- Publication Type:Original Article
- Keywords: HLA-A*33; 03; HPV 16 E7; immunotherapy; cervical cancer; epitopes
- MeSH: Amino Acid Sequence; CD8-Positive T-Lymphocytes/immunology/metabolism; Epitopes/*immunology/therapeutic use; Female; *HLA-A Antigens; Human papillomavirus 16/*immunology; Humans; *Immunotherapy; Interferon-gamma/analysis/*biosynthesis; Leukocytes, Mononuclear/immunology/metabolism; T-Lymphocytes, Cytotoxic/immunology/metabolism; Uterine Cervical Neoplasms/*therapy
- From:Yonsei Medical Journal 2017;58(1):43-50
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
