Patient-specific tumor antigen–MHC complex

Patient-specific tumor antigen–MHC complexes are individualized molecular complexes formed by the binding of unique tumor-derived antigens (including neoantigens generated by somatic mutations, fusion proteins, or aberrant post-translational modifications) to a patient's autologous major histocompatibility complex (MHC, typically class I or II) molecules. These complexes present on the surface of tumor cells and are recognized by T cell receptors, triggering a specific immune response directed against the tumor. They constitute the molecular targets for many forms of personalized immunotherapy, such as neoantigen vaccines and TCR-based cellular therapies. By exploiting these complexes, immune therapies aim to selectively eliminate tumor cells while sparing normal tissues. Their precision, however, is limited by tumor heterogeneity, variability in antigen processing and presentation, and the potential for immune escape through downregulation or loss of either antigen or MHC expression.

Other names

Personalized tumor antigen–MHC complexNeoantigen–MHC complexCustom tumor peptide–MHC complexTumor-associated antigen–MHC complex

Drugs and cell therapies targeting these complexes rely on: Recognition of neoantigen–MHC complexes by cytotoxic T lymphocytes, leading to selective killing of tumor cells. Enhancement or restoration of immune response by preventing tumor immune escape via checkpoint inhibition. Ex vivo expansion of T cells specific for patient neoantigen–MHC complexes, then reinfusion into the patient.