Telomerase reverse transcriptase peptide 540–HLA-A*02:01 complex (TERT540/HLA-A*02:01)

The TERT540 peptide–HLA-A*02:01 complex is a tumor-associated antigen (TAA) presented on the surface of malignant cells, consisting of a nonameric peptide (ILAKFLHWL) derived from human telomerase reverse transcriptase (hTERT) bound to the HLA-A*02:01 Major Histocompatibility Complex (MHC) class I molecule (Vonderheide et al., 1999, Immunity). hTERT is a critical enzyme for telomere maintenance and is overexpressed in approximately 85-90% of human cancers, providing a mechanism for replicative immortality (Shay & Wright, 2019, StatPearls). Because hTERT expression is highly restricted in most adult somatic tissues, this complex serves as a specific target for cancer immunotherapy. Therapeutic approaches targeting this complex include peptide-based vaccines like VX-001, which utilizes an optimized version of the TERT540 peptide to induce endogenous cytotoxic T-lymphocyte (CTL) responses (Slovin, 2012, NIH). Additionally, advanced modalities such as TCR-engineered T-cell (TCR-T) therapies and TCR-like antibodies are being developed to directly target cells presenting this specific pMHC complex. Clinical applications span various indications, including lung cancer, prostate cancer, and melanoma. The primary goal of these therapies is to trigger immune-mediated destruction of tumor cells while minimizing damage to healthy tissues, although potential off-tumor effects on TERT-expressing stem cells remain a safety consideration.

Other names

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

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) activation against cells presenting the peptide-MHC complex.