The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes.
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.
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. vonder@mbcrr.harvard.edu
R H
RH
Vonderheide
W C
WC
Hahn
J L
JL
Schultze
L M
LM
Nadler
D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D020134:Catalytic Domain / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D012313:RNA; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology; D019098:Telomerase / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D010455:Peptides; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase