Identificaiton of Novel Immunogenic Human Papillomavirus Type 16 E7-Specific Epitopes Restricted to HLA-A*33;03 for Cervical Cancer Immunotherapy
Yonsei Medical Journal 2017³â 58±Ç 1È£ p.43 ~ p.50
±è¼ºÈÆ(Kim Sung-Hoon) - Yonsei University College of Medicine Department of Obstetrics and Gynecology
Á¤Çý¿ø(Chung Hye-Won) - Yonsei University College of Medicine Department of Laboratory Medicine
°øÈÆ¿µ(Kong Hoon-Young) - Yonsei University College of Medicine Department of Laboratory Medicine
ÀÓÁ¾¹é(Lim Jong-Baeck) - Yonsei University College of Medicine Department of Laboratory Medicine
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-¥ã (IFN-¥ã) 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-¥ã 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-¥ã 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.
Å°¿öµå
HLA-A*33,03, HPV 16 E7, immunotherapy, cervical cancer, epitopes
KMID :
0311120170580010043
¿ø¹® ¹× ¸µÅ©¾Æ¿ô Á¤º¸
µîÀçÀú³Î Á¤º¸
À¯È¿¼º°á°ú(Recomendation)
Thsy study identified novel HPV 16 E7 epitopes E761-69 and E767-76 for the HLA-A*33;03 allele and showed that E761-69- and E767-76-sensitized PBMC as well as CD8+ CTLs have an antitumor cytotoxic effect against cervical cancer cells