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

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase enzyme, which maintains telomere length and is essential for the replicative immortality of cancer cells [1]. While hTERT is silenced in most adult somatic tissues, it is overexpressed in approximately 85-90% of all human malignancies, making it a nearly universal tumor-associated antigen [2]. Peptide fragments derived from the hTERT protein are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) [3]. These hTERT peptide-MHC complexes serve as specific targets for T-cell receptors (TCRs) on cytotoxic and helper T cells [4]. Therapeutic interventions, such as peptide vaccines (e.g., UV1, GV1001) and TCR-engineered T-cell therapies, aim to exploit this presentation to induce a robust anti-tumor immune response [5]. Because hTERT is critical for tumor cell survival, it is less prone to "antigen loss" compared to other targets, although potential toxicity to hTERT-expressing healthy stem cells remains a therapeutic challenge [6]. Sources: [1] Shay & Wright (2019) Seminars in Cancer Biology; [2] Kim et al. (1994) Science; [3] UniProtKB O14746; [4] Zanetti (2017) Nature Reviews Clinical Oncology; [5] Inderberg et al. (2022) JITC; [6] Buseman et al. (2012) Future Oncology.

Other names

hTERT epitopesTelomerase reverse transcriptase peptide-HLA complexhTERT-derived MHC-restricted peptideshTERT antigen-HLA complex

Induction of antigen-specific T-cell responses and cytotoxic T-lymphocyte-mediated lysis of hTERT-expressing tumor cells.