Tumor-associated peptide-major histocompatibility complex (pMHC) (pMHC)

Tumor-associated peptide-major histocompatibility complexes (pMHCs) are molecular assemblies on the cell surface consisting of a short peptide fragment derived from an intracellular tumor antigen bound to a Major Histocompatibility Complex (MHC) molecule (Source: Nature Reviews Immunology, 2021). These complexes serve as the specific ligands recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, enabling the immune system to identify and destroy malignant cells (Source: Journal of Hematology & Oncology, 2021). In modern immunotherapy, pMHCs are the primary targets for TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers like Tebentafusp, which are designed to bypass natural immune tolerance (Source: FDA, 2022). By targeting pMHCs, these therapies can address intracellular oncogenic proteins that are not accessible to traditional antibody-based drugs (Source: The Lancet, 2024). However, the clinical application of pMHC-targeting agents requires precise patient selection based on HLA typing and target antigen expression to ensure efficacy and minimize the risk of lethal off-target cross-reactivity with similar peptides in healthy tissues (Source: Science Translational Medicine, 2013).

Other names

TA-pMHCHLA-peptide complexAntigen-MHC complexTumor-specific MHC-peptide complexMHC-restricted antigen

Redirection of T-cell cytotoxicity through high-affinity binding of engineered T-cell receptors (TCRs) or TCR-mimetic antibodies to specific peptide-MHC complexes on the tumor cell surface.