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Cytotoxic T cell immunity against telomerase reverse transcriptase in humans
1Departments of Medicine and Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0368, USA.
Summary
Telomerase reverse transcriptase (hTRT) peptides can stimulate cytotoxic T lymphocytes (CTL) in cancer patients and healthy individuals. These hTRT-specific CTL can target various cancer cells, suggesting hTRT as a potential universal cancer vaccine.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Telomerase is a ribonucleoprotein enzyme associated with malignant transformation.
- Elevated telomerase activity is observed in most human tumors.
- Telomerase peptides presented by MHC Class I molecules may target cytotoxic T lymphocytes (CTL) to tumors.
Purpose of the Study:
- To investigate the potential of telomerase reverse transcriptase (hTRT) peptides as targets for cancer vaccines.
- To determine if precursor CTL recognizing hTRT peptides exist in normal individuals and cancer patients.
- To assess the efficacy of hTRT-specific CTL in lysing various cancer cell lines.
Main Methods:
- In vitro immunization of normal individuals and prostate cancer patients with HLA-A2.1 restricted hTRT peptides.
- Assessment of hTRT-specific CTL induction and characterization.
- In vivo immunization of HLA-A2.1 transgenic mice with hTRT peptides.
- Evaluation of cancer cell line lysis by generated CTL.
Main Results:
- The majority of individuals, including cancer patients, developed hTRT-specific CTL after in vitro immunization.
- CTL from cancer patients effectively lysed a variety of HLA-A2(+) cancer cell lines.
- In vivo immunization in mice generated a specific CTL response against hTRT peptides.
Conclusions:
- Precursor CTL for hTRT exist in normal individuals and cancer patients.
- hTRT-specific CTL demonstrate the capacity to recognize and lyse diverse tumor cells.
- hTRT holds promise as a potential universal cancer vaccine target.