Human telomerase reverse transcriptase 540-548 epitope presented by HLA-A*0201 (hTERT 540-548/HLA-A*0201)

The Human telomerase reverse transcriptase (hTERT) 540-548 epitope presented by HLA-A*0201 is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. hTERT is the catalytic subunit of telomerase, an enzyme responsible for maintaining telomere length, which is overexpressed in more than 85% of human cancers but has limited expression in most normal adult tissues [1][2]. The specific nonameric peptide sequence (ILAKFLHWL) is processed and presented on the cell surface by the HLA-A*0201 molecule, making it a recognizable target for CD8+ cytotoxic T lymphocytes [1]. Therapeutic strategies targeting this complex include peptide vaccines, such as Vx-001, and adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize this specific pMHC [3][4]. Because hTERT is essential for the immortalization of cancer cells and is widely expressed across different tumor types, it is considered a nearly universal tumor-associated antigen [2]. However, clinical development must account for potential off-target effects on healthy hTERT-expressing cells, such as hematopoietic stem cells and basal keratinocytes [5]. Sources: [1] Vonderheide, R. H., et al. (1999). The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity. [2] Shay, J. W., & Wright, W. E. (2006). Telomerase: a target for cancer therapeutics. Cancer Cell. [3] Giorguliani, S., et al. (2013). Vx-001, a therapeutic cancer vaccine. Expert Opinion on Biological Therapy. [4] Rosati, S. F., et al. (2014). A novel murine model for the study of hTERT-targeted immunotherapy. Cancer Immunology, Immunotherapy. [5] Buseman, C. M., et al. (2012). Is telomerase a viable target in cancer? Mutation Research.

Other names

hTERT (540-548)ILAKFLHWL peptidehTERT540HLA-A*02:01-hTERT(540-548)Telomerase reverse transcriptase (540-548)

The target is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, leading to the selective lysis of hTERT-expressing tumor cells. Therapeutic approaches include active immunization with peptide vaccines (e.g., Vx-001, which uses an optimized YLAKFLHWL variant to increase MHC affinity) or passive immunization via adoptive transfer of T cells engineered with high-affinity TCRs specific for the hTERT 540-548/HLA-A*0201 complex [1][3].