Human telomerase reverse transcriptase peptide-HLA-A*02:01 complex (hTERT/HLA-A2)

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase enzyme, which is responsible for maintaining telomere length and is overexpressed in approximately 85-90% of all human cancers (Vonderheide, 2002). In contrast, its expression is highly restricted in most normal adult somatic tissues, making it an ideal tumor-associated antigen (TAA). Peptides derived from the hTERT protein are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, specifically the HLA-A*02:01 allele, which is common in many populations (Vonderheide et al., 1999). These peptide-MHC complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the tumor. Therapeutic approaches targeting these complexes include peptide vaccines such as UV1 and GV1001, as well as adoptive cell therapies using TCR-engineered T cells (Lilleby et al., 2017; Brunsvig et al., 2006). While generally well-tolerated, a primary safety concern is the potential for "on-target, off-tumor" effects on normal telomerase-active cells, such as hematopoietic stem cells, though clinical evidence suggests a wide therapeutic window.

Other names

hTERT-derived HLA-A2-restricted epitopeshTERT/MHC class I complexTelomerase reverse transcriptase-derived HLA-A2-binding peptideshTERT540-548/HLA-A2hTERT865-873/HLA-A2

Induction of a T-cell mediated immune response where cytotoxic T lymphocytes recognize hTERT-derived peptides presented by HLA-A2 on tumor cells, leading to targeted cell lysis (Vonderheide, 2002).