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: Hong Guo, Jia Hao, Chao Wu, Yun Shi, Xiao-yan Zhao, Dian-chun Fang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 357 Issue 4 Pg. 1090-5 (Jun 15 2007) ISSN: 0006-291X [Print] United States
• PMID: 17462602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nucleotides
• Peptides
• Vaccines, DNA
• Vaccines, Subunit
• Telomerase

Topics

• Animals
• Cells, Cultured
• Female
• Immunity, Innate (drug effects, immunology)
• Mice
• Mice, Transgenic
• Nucleotides (administration & dosage)
• Peptides (administration & dosage)
• T-Lymphocytes (drug effects, immunology)
• Telomerase (administration & dosage, genetics)
• Vaccines, DNA (administration & dosage)
• Vaccines, Subunit (administration & dosage)