PMID- 21918960
OWN - NLM
STAT- MEDLINE
DCOM- 20120518
LR  - 20131121
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 8
DP  - 2012 Apr 15
TI  - Identification of novel immunogenic human leukocyte antigen-A 2402-binding 
      epitopes of human papillomavirus type 16 E7 for immunotherapy against human 
      cervical cancer.
PG  - 2173-83
LID - 10.1002/cncr.26468 [doi]
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-gamma (IFN-gamma) 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-gamma 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-gamma 
      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.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Jang, Sunphil
AU  - Jang S
AD  - Department of Laboratory Medicine, Yonsei University Medical College, Seoul, 
      Republic of Korea.
FAU - Kim, Young Tae
AU  - Kim YT
FAU - Chung, Hye Won
AU  - Chung HW
FAU - Lee, Kyoung-Ryul
AU  - Lee KR
FAU - Lim, Jong-Baeck
AU  - Lim JB
FAU - Lee, Kyungwon
AU  - Lee K
LA  - eng
PT  - Journal Article
DEP - 20110914
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Cisplatin/therapeutic use
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - HLA-A24 Antigen/*immunology
MH  - Human papillomavirus 16/*immunology
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - Papillomavirus E7 Proteins/*immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Uterine Cervical Neoplasms/immunology/*therapy/virology
EDAT- 2011/09/16 06:00
MHDA- 2012/05/19 06:00
CRDT- 2011/09/16 06:00
PHST- 2011/04/27 00:00 [received]
PHST- 2011/06/23 00:00 [revised]
PHST- 2011/06/30 00:00 [accepted]
PHST- 2011/09/16 06:00 [entrez]
PHST- 2011/09/16 06:00 [pubmed]
PHST- 2012/05/19 06:00 [medline]
AID - 10.1002/cncr.26468 [doi]
PST - ppublish
SO  - Cancer. 2012 Apr 15;118(8):2173-83. doi: 10.1002/cncr.26468. Epub 2011 Sep 14.