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The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes

R H Vonderheide1, W C Hahn, J L Schultze

  • 1Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. vonder@mbcrr.harvard.edu

Immunity
|July 14, 1999
PubMed

Insights

Telomerase (hTERT) is a tumor-associated antigen found in most cancers but not normal tissues. This discovery offers a promising target for developing effective cancer immunotherapies against a broad range of tumors.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor-associated antigens (TAA) are key targets for cancer immunotherapy.
  • Existing TAAs are often limited to specific cancer types and not universally expressed.
  • Novel TAAs with broader applicability are needed for effective cancer treatment.

Purpose of the Study:

  • To identify and characterize a widely expressed tumor-associated antigen for cancer immunotherapy.
  • To evaluate the potential of the telomerase catalytic subunit (hTERT) as a TAA.
  • To assess the ability of hTERT to elicit antitumor cytotoxic T lymphocyte (CTL) responses.

Main Methods:

  • Analysis of telomerase activity across various human cancers and normal tissues.
  • Identification of hTERT peptides as targets for T-cell recognition.
  • In vitro assessment of CTL-mediated lysis of hTERT-expressing tumors in a human system.

Main Results:

  • Telomerase activity is detected in over 85% of human cancers, with minimal expression in normal adult tissues.
  • hTERT-specific CD8+ cytotoxic T lymphocytes (CTLs) were generated.
  • These CTLs demonstrated lysis of tumors from multiple histologies that express hTERT and are restricted by MHC HLA-A2.

Conclusions:

  • The telomerase catalytic subunit (hTERT) is a broadly expressed tumor-associated antigen.
  • hTERT is a viable target for antigen-specific cancer immunotherapy.
  • hTERT-based immunotherapies hold potential for treating a wide spectrum of human cancers.

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