T cell receptor for human telomerase reverse transcriptase peptide–major histocompatibility complex (hTERT-TCR)

The T cell receptor (TCR) for human telomerase reverse transcriptase (hTERT) peptide–major histocompatibility complex (MHC) is a specialized immune receptor that recognizes fragments of the hTERT protein presented on the surface of cells (Vonderheide, 2002). hTERT is the catalytic subunit of telomerase, an enzyme that is overexpressed in approximately 85-90% of all human cancers to maintain telomere length and facilitate cellular immortality, while remaining largely absent in healthy adult somatic cells (Shay & Wright, 2011). This makes the hTERT-MHC complex a nearly universal tumor-associated antigen (TAA). Therapeutic strategies involving this receptor primarily focus on TCR-engineered T cell (TCR-T) therapies, where a patient's T cells are modified to express a high-affinity TCR specific for hTERT peptides, typically in the context of HLA-A*02:01. Upon binding to the target complex, these engineered T cells initiate a potent cytotoxic response against the tumor (Mizukoshi et al., 2019). While promising, the development of these therapies must account for potential on-target, off-tumor effects, as hTERT is expressed in certain regenerative tissues like hematopoietic stem cells, which could lead to myelosuppression (Schröder et al., 2001).

Other names

hTERT-specific T-cell receptorTelomerase-specific TCRhTERT-MHC targeting receptorTERT-specific TCRhTERT-specific TCR

Engineered T cells expressing the TCR bind to hTERT peptides presented by MHC molecules on the surface of cancer cells, triggering T-cell activation, cytokine release, and direct lysis of the target cell.