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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
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.
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.