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Title: A novel peptide-nucleotide dual vaccine of human telomerase reverse transcriptase induces a potent cytotoxic T-cell response in vivo

Abstract

Human telomerase reverse transcriptase (hTERT) is highly expressed in over 85% of human cancers, which makes it a broadly applicable molecular target for cancer therapy. Several groups have demonstrated that hTERT can efficiently evoke specific cytotoxic T lymphocytes (CTL) responses for malignant tumors. In the present study, we developed a novel virus-like particulate peptide-nucleotide dual vaccine (PNDV) of hTERT, which was composed of a low-affinity epitope variant with encoding full-length gene in the same virus-size particulate. We verified the formation of PNDV by DNA retarding assay, DNase I protection assay and transmission electron microscopy, and confirmed its immunogenicity and transfection activities in mammalian cells. Furthermore, in vivo immunization of HLA-A2.1 transgenic mice generated efficient IFN-{gamma} secretion and hTERT-specific CTLs which are known to cause selective cell death of telomerase positive gastrointestinal cancer cells. To our knowledge, this represents the first report on collocating a low-affinity epitope variant with a full-length hTERT gene for anti-cancer vaccine design. This novel strategy for vaccine design not only enables enhanced immunity to a universal tumor antigen, but also has the potential to generate CTLs effective in telomerase-positive tumor cells of diverse tissue origins. Therefore, our findings bear significant implications for immunotherapy of human cancers.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1]
  1. Institute of Gastroenterology of PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)
Publication Date:
OSTI Identifier:
20991389
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 357; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.04.056; PII: S0006-291X(07)00778-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; DNA; IMMUNOTHERAPY; IN VIVO; LYMPHOCYTES; NEOPLASMS; NUCLEOTIDES; PEPTIDES; TRANSGENIC MICE; TRANSMISSION ELECTRON MICROSCOPY; VACCINES; VIRUSES

Citation Formats

Guo, Hong, Hao, Jia, Wu, Chao, Shi, Yun, Zhao, Xiao-yan, and Fang, Dian-chun. A novel peptide-nucleotide dual vaccine of human telomerase reverse transcriptase induces a potent cytotoxic T-cell response in vivo. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.04.056.
Guo, Hong, Hao, Jia, Wu, Chao, Shi, Yun, Zhao, Xiao-yan, & Fang, Dian-chun. A novel peptide-nucleotide dual vaccine of human telomerase reverse transcriptase induces a potent cytotoxic T-cell response in vivo. United States. doi:10.1016/j.bbrc.2007.04.056.
Guo, Hong, Hao, Jia, Wu, Chao, Shi, Yun, Zhao, Xiao-yan, and Fang, Dian-chun. Fri . "A novel peptide-nucleotide dual vaccine of human telomerase reverse transcriptase induces a potent cytotoxic T-cell response in vivo". United States. doi:10.1016/j.bbrc.2007.04.056.
@article{osti_20991389,
title = {A novel peptide-nucleotide dual vaccine of human telomerase reverse transcriptase induces a potent cytotoxic T-cell response in vivo},
author = {Guo, Hong and Hao, Jia and Wu, Chao and Shi, Yun and Zhao, Xiao-yan and Fang, Dian-chun},
abstractNote = {Human telomerase reverse transcriptase (hTERT) is highly expressed in over 85% of human cancers, which makes it a broadly applicable molecular target for cancer therapy. Several groups have demonstrated that hTERT can efficiently evoke specific cytotoxic T lymphocytes (CTL) responses for malignant tumors. In the present study, we developed a novel virus-like particulate peptide-nucleotide dual vaccine (PNDV) of hTERT, which was composed of a low-affinity epitope variant with encoding full-length gene in the same virus-size particulate. We verified the formation of PNDV by DNA retarding assay, DNase I protection assay and transmission electron microscopy, and confirmed its immunogenicity and transfection activities in mammalian cells. Furthermore, in vivo immunization of HLA-A2.1 transgenic mice generated efficient IFN-{gamma} secretion and hTERT-specific CTLs which are known to cause selective cell death of telomerase positive gastrointestinal cancer cells. To our knowledge, this represents the first report on collocating a low-affinity epitope variant with a full-length hTERT gene for anti-cancer vaccine design. This novel strategy for vaccine design not only enables enhanced immunity to a universal tumor antigen, but also has the potential to generate CTLs effective in telomerase-positive tumor cells of diverse tissue origins. Therefore, our findings bear significant implications for immunotherapy of human cancers.},
doi = {10.1016/j.bbrc.2007.04.056},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 357,
place = {United States},
year = {2007},
month = {6}
}