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

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase enzyme, which is overexpressed in approximately 85-90% of all human cancers while remaining largely absent in most normal adult somatic cells (Kim et al., 1994; Shay & Wright, 2019). This differential expression makes hTERT-derived peptides, when presented on the cell surface by Human Leukocyte Antigen (HLA) Class I or Class II molecules, highly attractive targets for cancer immunotherapy (Vonderheide, 2002). These peptide-HLA complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes and CD4+ helper T cells, respectively. Therapeutic strategies targeting these complexes include peptide vaccines, such as GV1001 and UV1, as well as engineered TCR-T cell therapies designed to specifically bind the hTERT-HLA interface (Bernhardt et al., 2006; Inderberg et al., 2022). By activating the immune system against cells presenting these complexes, these therapies aim to selectively eliminate malignant cells that rely on telomerase for replicative immortality. However, challenges remain regarding the potential for on-target off-tumor effects in telomerase-positive healthy tissues, such as hematopoietic stem cells and germ cells (Mizukoshi & Kaneko, 2019).

Other names

hTERT-MHC complexTelomerase-derived peptide-HLA complexhTERT antigen-HLA complexhTERT-HLA-A2 complex

Stimulation of peptide-specific T-cell receptors (TCRs) on CD8+ or CD4+ T cells to induce an anti-tumor immune response against cells overexpressing telomerase (Vonderheide, 2002; Inderberg et al., 2022).