T-cell receptor recognizing human telomerase reverse transcriptase (hTERT)-derived peptide–MHC complexes (hTERT-specific TCR)

The T-cell receptor (TCR) recognizing human telomerase reverse transcriptase (hTERT)-derived peptide–MHC complexes is a specialized immune receptor used in TCR-engineered T-cell (TCR-T) therapy to target malignant cells. hTERT is the catalytic subunit of telomerase, an enzyme responsible for maintaining telomere length, which is overexpressed in over 85% of human cancers to enable replicative immortality (Source: PubMed, PMID: 28923834). Because hTERT expression is minimal in most adult somatic tissues, it serves as a nearly universal tumor-associated antigen (TAA). TCRs specific for hTERT peptides, such as those restricted by HLA-A*02:01, allow T-cells to identify and eliminate cancer cells presenting these fragments on their surface (Source: NIH, ClinicalTrials.gov). Upon recognition of the peptide-MHC complex, the TCR initiates a signaling cascade that leads to T-cell activation, cytokine production, and the direct lysis of the tumor cell. Clinical development of these TCRs focuses on treating a wide range of solid and hematological malignancies, though researchers must monitor for potential on-target, off-tumor toxicities in hTERT-positive healthy tissues like bone marrow and the gastrointestinal tract (Source: Journal of Immunotherapy, 2021). This target represents a significant opportunity for broad-spectrum cancer immunotherapy due to the prevalence of telomerase activity in diverse tumor types.

Other names

hTERT-TCRTelomerase-specific T-cell receptorhTERT-targeted TCRhTERT-specific T-cell receptorTCR targeting hTERT/HLA complexes

Engineered T-cells expressing the hTERT-specific TCR bind to hTERT peptide-MHC complexes on the surface of cancer cells, triggering T-cell signaling, cytokine release, and directed killing of the target cell.