Conclusion
We identified E7₅&sub0;₋₅₉ and E7₅&sub2;₋₆&sub1; 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.
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 &sup5;¹Cr release assay with SNU1299 cells.
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
Results
Among the fourteen 15-amino acid peptides, E7&sub4;₉₋₆&sub3; (RAHYNIVTFCCKCDS) demonstrated the highest IFN-γ production from peripheral blood mononuclear cells (PBMCs), and CD8+ CTLs sensitized with E7&sub4;₉₋₆&sub3; 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 E7&sub4;₉₋₆&sub3;, E7₅&sub0;₋₅₉ (AHYNIVTFCC), and E7₅&sub2;₋₆&sub1; (YNIVTFCCKC) induced significantly higher IFN-γ production and cytotoxic effects against SNU1299 cells than the other peptides and negative controls, and the cytotoxicity of E7₅&sub0;₋₅₉- and E7₅&sub2;₋₆&sub1;-sensitized PBMCs was induced via the cytolytic effect of CD8+ CTLs.