Human telomerase reverse transcriptase (hTERT) peptide-MHC class I complex (hTERT-pMHC-I)

Human telomerase reverse transcriptase (hTERT) peptide-MHC class I complexes represent a critical class of universal tumor-associated antigens (TAAs). hTERT is the catalytic subunit of the telomerase enzyme, which is overexpressed in approximately 85-90% of all human cancers to maintain telomere length and replicative immortality, while remaining largely absent in most somatic tissues (Kim et al., Science, 1994). Short peptide fragments derived from the hTERT protein are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, where they can be recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (Vonderheide, Nature Reviews Cancer, 2002). This presentation makes hTERT an attractive target for various immunotherapeutic strategies, including cancer vaccines such as UV1 and GV1001, as well as TCR-engineered T-cell therapies (Ultimovacs, 2023; GemVax, 2023). Because hTERT expression is essential for the survival of most cancer cells, targeting these peptide-MHC complexes may limit the potential for tumor antigen loss as a mechanism of immune escape. However, therapeutic development must account for the low-level expression of hTERT in certain normal regenerative tissues, such as hematopoietic stem cells and germ cells, which poses a theoretical risk of on-target off-tumor toxicity. Clinical trials have generally shown these therapies to be well-tolerated, with efficacy often correlating with the induction of robust hTERT-specific T-cell responses.

Other names

hTERT-derived epitopesTelomerase-derived peptideshTERT antigenhTERT/HLA complexhTERT-pMHC

Induction of peptide-specific cytotoxic T-lymphocyte (CTL) responses through T-cell receptor (TCR) recognition of the hTERT peptide-MHC class I complex on the surface of tumor cells.