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

Sunphil Jang, YoungTae Kim, Hye Won Chung, Kyoung Ryul Lee, Jong Baeck Lim, Kyungwon Lee

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: Among 14 overlapping 15-amino acid peptides, E7 61-75 (CDSTLRLCVQSTHVD) and E7 67-81 (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 E7 61-75 and E7 67-81 were synthesized. E7 61-69 (CDSTLRLCV) and E7 67-76 (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. E7 61-69 -sensitized and E7 67-76 -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 E7 67-76 -sensitized PBMCs in vivo. Conclusions: E7 61-69 and E7 67-76 were identified as novel HPV type 16 E7 epitopes for HLA-A*2402, which could be used for immunotherapy against cervical cancer.

Original languageEnglish
Pages (from-to)2173-2183
Number of pages11
JournalCancer
Volume118
Issue number8
DOIs
Publication statusPublished - 2012 Apr 15

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Human papillomavirus 16
HLA Antigens
Uterine Cervical Neoplasms
Immunotherapy
Epitopes
Cytotoxic T-Lymphocytes
Peptides
Blood Cells
Interferons
Papillomavirus E7 Proteins
Amino Acids
Nude Mice
Cisplatin
Flow Cytometry
Control Groups
Growth
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{d7ab535a95dc4967a0c4ca2027b81331,
title = "Identification of novel immunogenic human leukocyte antigen-A*2402- binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human cervical cancer",
abstract = "Background: 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. Methods: 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. Results: Among 14 overlapping 15-amino acid peptides, E7 61-75 (CDSTLRLCVQSTHVD) and E7 67-81 (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 E7 61-75 and E7 67-81 were synthesized. E7 61-69 (CDSTLRLCV) and E7 67-76 (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. E7 61-69 -sensitized and E7 67-76 -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 E7 67-76 -sensitized PBMCs in vivo. Conclusions: E7 61-69 and E7 67-76 were identified as novel HPV type 16 E7 epitopes for HLA-A*2402, which could be used for immunotherapy against cervical cancer.",
author = "Sunphil Jang and YoungTae Kim and Chung, {Hye Won} and Lee, {Kyoung Ryul} and Lim, {Jong Baeck} and Kyungwon Lee",
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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. / Jang, Sunphil; Kim, YoungTae; Chung, Hye Won; Lee, Kyoung Ryul; Lim, Jong Baeck; Lee, Kyungwon.

In: Cancer, Vol. 118, No. 8, 15.04.2012, p. 2173-2183.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of novel immunogenic human leukocyte antigen-A*2402- binding epitopes of human papillomavirus type 16 E7 for immunotherapy against human cervical cancer

AU - Jang, Sunphil

AU - Kim, YoungTae

AU - Chung, Hye Won

AU - Lee, Kyoung Ryul

AU - Lim, Jong Baeck

AU - Lee, Kyungwon

PY - 2012/4/15

Y1 - 2012/4/15

N2 - Background: 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. Methods: 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. Results: Among 14 overlapping 15-amino acid peptides, E7 61-75 (CDSTLRLCVQSTHVD) and E7 67-81 (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 E7 61-75 and E7 67-81 were synthesized. E7 61-69 (CDSTLRLCV) and E7 67-76 (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. E7 61-69 -sensitized and E7 67-76 -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 E7 67-76 -sensitized PBMCs in vivo. Conclusions: E7 61-69 and E7 67-76 were identified as novel HPV type 16 E7 epitopes for HLA-A*2402, which could be used for immunotherapy against cervical cancer.

AB - Background: 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. Methods: 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. Results: Among 14 overlapping 15-amino acid peptides, E7 61-75 (CDSTLRLCVQSTHVD) and E7 67-81 (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 E7 61-75 and E7 67-81 were synthesized. E7 61-69 (CDSTLRLCV) and E7 67-76 (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. E7 61-69 -sensitized and E7 67-76 -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 E7 67-76 -sensitized PBMCs in vivo. Conclusions: E7 61-69 and E7 67-76 were identified as novel HPV type 16 E7 epitopes for HLA-A*2402, which could be used for immunotherapy against cervical cancer.

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