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

Immunity. 1999 Jun;10(6):673-9. doi: 10.1016/s1074-7613(00)80066-7.

Abstract

The discovery of tumor-associated antigens (TAA) in certain human malignancies has prompted renewed efforts to develop antigen-specific immunotherapy of cancer. However, most TAA described thus far are expressed in one or a few tumor types, and, among patients with these types of tumors, TAA expression is not universal. Here, we characterize the telomerase catalytic subunit (hTERT) as a widely expressed TAA capable of triggering antitumor cytotoxic T lymphocyte (CTL) responses. More than 85% of human cancers exhibit strong telomerase activity, but normal adult tissues, with few exceptions, do not. In a human system, CD8+ CTL specific for an hTERT peptide and restricted to MHC HLA-A2 lysed hTERT+ tumors from multiple histologies. These findings identify hTERT as a potentially important and widely applicable target for anticancer immunotherapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / immunology
  • Catalytic Domain / immunology
  • Cytotoxicity, Immunologic
  • DNA-Binding Proteins
  • HLA-A Antigens / metabolism
  • HeLa Cells
  • Humans
  • Lymphocyte Activation
  • Peptides / immunology
  • Peptides / metabolism
  • RNA*
  • T-Lymphocytes, Cytotoxic / enzymology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Telomerase / biosynthesis*
  • Telomerase / immunology
  • Telomerase / metabolism
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • HLA-A Antigens
  • Peptides
  • telomerase RNA
  • RNA
  • Telomerase