A novel peptide-nucleotide dual vaccine of human telomerase reverse transcriptase induces a potent cytotoxic T-cell response in vivo.
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.
Guo
Hong
H
Institute of Gastroenterology of PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Hao
Jia
J
Wu
Chao
C
Shi
Yun
Y
Zhao
Xiao-yan
XY
Fang
Dian-chun
DC
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009711:Nucleotides / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D019098:Telomerase / Q000008:administration & dosage* / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage*; D022223:Vaccines, Subunit / Q000008:administration & dosage*
D009711:Nucleotides; D010455:Peptides; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D019098:Telomerase