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Identification of novel immunogenic human leukocyte antigen-A*2402-binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human cervical cancer
Article first published online: 14 SEP 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 8, pages 2173–2183, 15 April 2012
How to Cite
Jang, S., Kim, Y. T., Chung, H. W., Lee, K.-R., Lim, J.-B. and Lee, K. (2012), Identification of novel immunogenic human leukocyte antigen-A*2402-binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human cervical cancer. Cancer, 118: 2173–2183. doi: 10.1002/cncr.26468
- Issue published online: 6 APR 2012
- Article first published online: 14 SEP 2011
- Manuscript Accepted: 30 JUN 2011
- Manuscript Revised: 23 JUN 2011
- Manuscript Received: 27 APR 2011
- HPV 16 E7;
- cervical cancer;
A study was undertaken to identify new immunogenic human leukocyte antigen (HLA)-A*2402-restricted epitopes from human papillomavirus (HPV) type 16 E7 protein for immunotherapy against cervical cancer.
Synthetic overlapping peptides were screened by measuring the frequency of CD8+ cytotoxic T lymphocytes (CTLs) producing intracellular interferon-γ (IFN-γ) using flow cytometry and were validated in SiHa cells with a Cr release cytotoxicity assay. In vivo antitumor effects of peptide-sensitized peripheral blood mononuclear cells (PBMCs) and isolated CD8+ CTLs were evaluated using BALB/c nude mice with SiHa cell xenotransplants.
Among 14 overlapping 15-amino acid peptides, E761-75(CDSTLRLCVQSTHVD) and E767-81(LCVQSTHVDIRTLED) induced significantly higher IFN-γ production (P < .05) and showed higher in vitro cytotoxicity against SiHa cells than did cells sensitized with the negative control. To determine the exact HLA-A*2402-restricted epitopes, a total of 25 overlapping 9- or 10-amino acid peptides spanning E761-75 and E767-81 were synthesized. E761-69(CDSTLRLCV) and E767-76(LCVQSTHVDI) induced significantly greater IFN-γ production as well as increased in vitro cytotoxicity against SiHa cells compared with those of other peptides and the negative control (P < .01), and the antitumor effects of these peptide-sensitized PBMCs were induced by CD8+ CTLs. E761-69-sensitized and E767-76-sensitized PBMCs and isolated CD8+ CTLs showed a much greater suppression of tumor growth in vivo compared with that of control groups treated with PBS (P < .01). The authors also confirmed the synergistic antitumor effect of cisplatin followed by E767-76-sensitized PBMCs in vivo.
E761-69 and E767-76 were identified as novel HPV type 16 E7 epitopes for HLA-A*2402, which could be used for immunotherapy against cervical cancer. Cancer 2012. © 2011 American Cancer Society.