Major histocompatibility complex presenting human telomerase reverse transcriptase-derived peptides (MHC-hTERT) (MHC-hTERT)

The Major histocompatibility complex (MHC) presenting human telomerase reverse transcriptase (hTERT)-derived peptides is a critical target in cancer immunotherapy [Zanetti, 2017]. hTERT is the catalytic subunit of telomerase, an enzyme that maintains telomere length and is overexpressed in approximately 85-90% of all human cancers, while remaining largely absent in normal somatic cells [Shay & Wright, 2019]. Within tumor cells, hTERT proteins are processed into peptides and loaded onto MHC class I or II molecules for presentation on the cell surface. This complex serves as a universal tumor-associated antigen that can be recognized by the T-cell receptors (TCRs) of cytotoxic and helper T-lymphocytes. Therapeutic approaches targeting this complex include vaccines designed to elicit an endogenous immune response and engineered TCR-T cell therapies for direct tumor targeting [Bernhardt et al., 2021]. While the target offers a broad therapeutic window, potential safety concerns include off-target effects on telomerase-positive healthy cells like hematopoietic stem cells [Mizukoshi & Kaneko, 2019]. Overall, the MHC-hTERT complex represents a promising avenue for treating a wide range of malignancies due to its high prevalence and essential role in cancer cell immortality.

Other names

HLA-hTERT complexhTERT peptide-MHC complexTelomerase-derived peptide-MHCpMHC-hTERThTERT-HLA complexhTERT-MHC class I complexhTERT-MHC class II complex

Therapeutic agents target this complex by either providing hTERT-derived peptides (via vaccines) to be processed and presented by host MHC molecules, or by utilizing engineered T-cell receptors (TCRs) that directly recognize and bind the pre-existing peptide-MHC complex on the surface of tumor cells, thereby inducing T-cell mediated cytotoxicity [Zanetti, 2017; Bernhardt et al., 2021].