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Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme, which maintains telomere length and is upregulated in approximately 85-90% of all human cancers (Source: National Cancer Institute). TERT-derived T-cell epitopes are peptide fragments presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, acting as targets for T-cell mediated immunity (Source: PubMed, PMID: 28633324). These epitopes are considered universal tumor-associated antigens because of their widespread expression in malignancies and limited presence in normal somatic tissues, primarily restricted to germ cells and stem cells (Source: UniProt, O14746). Therapeutic interventions such as the GV1001 and UV1 vaccines aim to stimulate the immune system to recognize these specific peptide-MHC complexes to eliminate cancer cells (Source: ClinicalTrials.gov, NCT03538314). Additionally, TCR-engineered T-cell therapies are being developed to provide high-affinity recognition of TERT epitopes presented by HLA-A*02:01 (Source: PubMed, PMID: 31515461). The essential role of TERT in maintaining cancer cell immortality makes these epitopes resilient targets against immune escape through antigen loss.
Induction of T-cell mediated cytotoxicity through the recognition of TERT peptides presented on MHC molecules. Vaccines (peptide, DNA, or dendritic cell-based) prime the immune system to recognize these epitopes, while TCR-engineered T cells are modified to bind them directly. Upon recognition, T cells release cytotoxic factors like granzymes and perforins to induce apoptosis in the target cancer cell (Source: PubMed, PMID: 30206110).
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