Human telomerase reverse transcriptase-derived peptide–human leukocyte antigen complex (hTERT peptide–HLA complex)

The human telomerase reverse transcriptase (hTERT)-derived peptide–human leukocyte antigen (HLA) complex is a prominent target in cancer immunotherapy due to the near-universal expression of telomerase in malignant cells. hTERT is the catalytic subunit of the telomerase enzyme, which maintains telomere length and confers replicative immortality to cancer cells; it is overexpressed in approximately 85-90% of all human cancers but is largely absent in most normal adult somatic cells (Kim et al., 2016, Cancer Immunology, Immunotherapy). Peptides derived from the hTERT protein are processed intracellularly and presented on the cell surface by HLA class I or II molecules, forming a complex that serves as a ligand for T-cell receptors (TCRs). This presentation allows the immune system to distinguish between normal and neoplastic cells. Therapeutic strategies targeting these complexes include peptide-based vaccines like GV1001 and UV1, which aim to prime the patient's own immune system, and adoptive cell therapies using TCR-engineered T cells designed for high-affinity binding to specific hTERT-HLA combinations (Inderberg et al., 2022, Frontiers in Immunology). Because hTERT is essential for tumor cell survival and proliferation, it is considered a highly stable target with a lower likelihood of antigen loss compared to other tumor-associated antigens.

Other names

hTERT-MHC complexTelomerase-derived peptide–HLA complexhTERT-HLA-A*0201 complexGV1001-HLA complexhTERT-derived peptide–MHC class I/II complexTERT-HLA complex

Therapeutic agents target this complex by either inducing an endogenous immune response (vaccines) or providing engineered T cells (TCR-T) that recognize the specific hTERT peptide presented by HLA molecules. Recognition by T-cell receptors (TCRs) triggers the release of cytotoxic granules (perforin/granzyme) and cytokines (IFN-gamma), leading to the selective lysis of telomerase-positive tumor cells (Zhu et al., 2021, Frontiers in Immunology).