Telomerase (hTERT 611-626) serves as a tumor antigen in B-cell chronic lymphocytic leukemia and generates spontaneously antileukemic, cytotoxic T cells

Exp Hematol. 2007 Feb;35(2):297-304. doi: 10.1016/j.exphem.2006.10.006.


Objective: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase. In B-cell chronic lymphocytic leukemia (B-CLL), telomerase activity is increased in about 75% of patients. The aim of this study was to analyze whether B-CLL patients with telomerase-positive leukemic cells had naturally occurring, telomerase-specific T cells that might be utilized for immune-mediated lysis of autologous tumor cells.

Methods: Spontaneous T-cell immunity and cytotoxicity against hTERT was explored in B-CLL. Nineteen of 25 B-CLL patients (76%) expressed hTERT (reverse transcriptase polymerase chain reaction) and 10 were selected for specific T-cell analysis against hTERT.

Results: The stimulation index (SI) of T cells from seven telomerase-positive patients stimulated with a 16aa hTERT peptide (611-626) loaded onto dendritic cells (DC) was 33.9 +/- 15.4 (mean SI +/- standard error of mean) and 13.2 +/- 5.6 against a Ras control peptide (p = 0.05), whereas the corresponding SI values for three telomerase-negative patients were 5.3 +/- 5.3 against the hTERT 611-626 peptide and 10.3 +/- 6.5 against the Ras peptide, respectively; and for three healthy controls, 5.4 +/- 0.9 against the hTERT 611-626 peptide and 4.5 +/- 1.0 against the Ras peptide (both not significant). Blocking experiments revealed that the specific responses were major histocompatibility complex (MHC) class I and MHC class II restricted. DC pulsed with the hTERT-peptide generated MHC class I-restricted, hTERT-specific cytotoxic T lymphocytes in six of seven telomerase-positive patients; mean cytotoxicity of hTERT-stimulated T cells was 49.8% +/- 9.3% vs 13.1 +/- 2.9% for Ras-stimulated T cells (p < 0.05). In three of three telomerase-negative patients, no hTERT-specific cytotoxic T lymphocytes could be expanded.

Conclusion: Telomerase-positive B-CLL patients have spontaneously occurring cytotoxic hTERT-specific T cells. This antigen might be explored as a therapeutic vaccine in B-CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / immunology*
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Profiling
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Male
  • Middle Aged
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Peptide Fragments / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • T-Lymphocytes, Cytotoxic / immunology*
  • Telomerase / genetics
  • Telomerase / immunology*
  • Telomerase / pharmacology


  • Antigens, Neoplasm
  • Histocompatibility Antigens Class I
  • Peptide Fragments
  • GV1001 peptide
  • Telomerase