Patient-specific tumor-associated peptide–major histocompatibility complex (pMHC)

Patient-specific tumor-associated peptide–major histocompatibility complex (pMHC) molecules are the fundamental units recognized by the adaptive immune system to identify and eliminate malignant cells. These complexes consist of a short peptide fragment, derived from either mutated proteins (neoantigens) or overexpressed tumor-associated antigens, which is loaded onto MHC molecules (Human Leukocyte Antigens or HLA in humans) and presented on the cell surface. In solid tumors, these pMHCs serve as highly specific targets for T-cell receptors (TCRs), allowing for the precise discrimination between cancerous and healthy tissue. Therapeutic strategies leveraging these targets include TCR-engineered T-cell therapies (TCR-T), personalized neoantigen vaccines, and bispecific T-cell engagers known as ImmTACs. Because many of these targets are derived from unique somatic mutations, they offer a pathway toward truly personalized immunotherapy with a high degree of specificity. However, the clinical utility of targeting pMHCs can be challenged by the tumor's ability to downregulate MHC expression or the potential for off-target cross-reactivity with healthy tissues presenting similar peptide sequences.

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexHLA-peptide complexTumor-associated antigen-MHC complexpMHC complex

Binding of T-cell receptors (TCRs) or TCR-mimetic antibodies to the peptide-MHC complex to trigger cytotoxic T-lymphocyte mediated lysis of tumor cells.