Tumor antigen-derived peptide-major histocompatibility complex (pMHC) (pMHC)

Tumor antigen-derived peptide-major histocompatibility complexes (pMHC) are the fundamental targets for T-cell-mediated cancer immunotherapies. These complexes are formed when intracellular proteins—including mutated neoantigens, overexpressed tumor-associated antigens, or cancer-germline antigens—are degraded into short peptide fragments and loaded onto Human Leukocyte Antigen (HLA) molecules for presentation on the cell surface (NIH, 2024). The recognition of these specific pMHC ligands by T-cell receptors (TCRs) is the critical step that triggers the adaptive immune system to destroy malignant cells. Modern therapeutic strategies, such as TCR-engineered T-cell (TCR-T) therapies and bispecific TCR-engagers like Tebentafusp, are designed to bypass natural immune tolerance by providing high-affinity recognition of these complexes (FDA, 2022). Additionally, personalized cancer vaccines aim to prime the endogenous immune system to recognize patient-specific neoantigen-MHC complexes (PubMed: 33461153). Despite their high specificity, these targets present challenges including the requirement for specific patient HLA genotypes and the risk of immune escape through HLA downregulation or loss of heterozygosity in the tumor microenvironment.

Other names

Tumor antigen-HLA complexNeoantigen-MHC complexPeptide-MHC complexpMHCpHLATumor-specific antigen-MHC complexCancer-associated peptide-MHC

Recognition by engineered or endogenous T-cell receptors (TCRs) or TCR-mimetic antibodies to trigger T-cell mediated cytotoxicity against tumor cells.