Identification of novel immunogenic human leukocyte antigen-A*2402-binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human 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.