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hTERT-derived peptide–HLA complexes are tumor-associated antigens formed when the human telomerase reverse transcriptase (hTERT) protein is proteolytically processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (1.2.1). hTERT is the catalytic subunit of telomerase, an enzyme essential for telomere maintenance and cellular immortality, and is overexpressed in over 85-90% of human cancers while being largely absent in most normal somatic cells (1.2.1, 1.3.1). This differential expression makes these complexes prime targets for cancer immunotherapies, including peptide vaccines like UV1 and GV1001, as well as adoptive T-cell therapies and T-cell engagers (1.1.1, 1.2.1, 1.3.3). Therapeutic strategies aim to stimulate cytotoxic T lymphocytes (CTLs) to recognize these specific peptide-HLA signatures and selectively lyse tumor cells (1.2.1, 1.2.3). Despite their promise, challenges remain regarding the natural presentation levels of certain epitopes and the potential for on-target off-tumor effects on hTERT-expressing normal tissues such as bone marrow stem cells (1.2.2, 1.2.4, 1.3.1).
Induction of T-cell mediated cytotoxicity against tumor cells by enabling the recognition of hTERT-derived peptides presented on HLA molecules by the T-cell receptor (TCR).
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