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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
Yonsei Medical Journal ; : 43-50, 2017.
Article in English | WPRIM | ID: wpr-65064
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Leukocytes, Mononuclear / T-Lymphocytes, Cytotoxic / HLA-A Antigens / Uterine Cervical Neoplasms / Amino Acid Sequence / Interferon-gamma / CD8-Positive T-Lymphocytes / Human papillomavirus 16 / Immunotherapy / Epitopes Type of study: Diagnostic study Limits: Female / Humans Language: English Journal: Yonsei Medical Journal Year: 2017 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Leukocytes, Mononuclear / T-Lymphocytes, Cytotoxic / HLA-A Antigens / Uterine Cervical Neoplasms / Amino Acid Sequence / Interferon-gamma / CD8-Positive T-Lymphocytes / Human papillomavirus 16 / Immunotherapy / Epitopes Type of study: Diagnostic study Limits: Female / Humans Language: English Journal: Yonsei Medical Journal Year: 2017 Type: Article