Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor

Clin Cancer Res. 2012 Nov 15;18(22):6284-95. doi: 10.1158/1078-0432.CCR-12-0896. Epub 2012 Oct 2.


Purpose: To evaluate CD4(+) helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT).

Experimental design: To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice were used to study the CD4(+) helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A*0201-positive B16 melanoma that express TERT.

Results: The presence of a high number of UCP-specific CD4(+) T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF-α. In HLA transgenic mice, UCP vaccinations induced high avidity CD4(+) T(H)1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8(+) T cells.

Conclusions: Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / physiology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Humans
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / physiology
  • Telomerase / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / physiology
  • Xenograft Model Antitumor Assays


  • Cancer Vaccines
  • Peptide Fragments
  • TERT protein, human
  • Telomerase