Telomerase reverse transcriptase peptide 540-548 presented by Human leukocyte antigen A*02:01 (TERT540/HLA-A*02:01)

The TERT540 peptide presented in HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target utilized in the development of cancer immunotherapies. The peptide sequence, ILAKFLHWL, corresponds to residues 540-548 of the human telomerase reverse transcriptase (hTERT) protein, which is the catalytic component of the telomerase enzyme complex (PubMed: 10491287). Telomerase is overexpressed in approximately 85-90% of all human cancers, where it facilitates replicative immortality, but it remains largely absent in normal somatic tissues (PubMed: 24651523). This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes when presented on the surface of cells by the HLA-A*02:01 allele. Therapeutic strategies targeting this pMHC include peptide vaccines like VX-001, which uses an optimized version of the TERT540 peptide to enhance immunogenicity, and adoptive T-cell therapies employing engineered TCRs (PubMed: 30103341). Clinical investigations have targeted various malignancies, including non-small cell lung cancer and prostate cancer, though challenges such as immune evasion and the potential for low-level expression in healthy stem cells remain considerations for safety and efficacy (PubMed: 26156614).

Other names

hTERT 540-548ILAKFLHWL-HLA-A*02:01 complexTERT-540hTERT(540-548) peptide-MHC complexTelomerase reverse transcriptase (540-548) presented by HLA-A2

Active immunotherapy via vaccination to induce peptide-specific CD8+ T-cell responses; Adoptive cell transfer using T-cell receptor (TCR) engineered T-cells designed to recognize the pMHC complex.