Tumor-specific mutant peptide–human leukocyte antigen complex

The tumor-specific mutant peptide–human leukocyte antigen (HLA) complex is a cell-surface molecular complex formed when a peptide derived from a somatic mutation in a tumor (a neoantigen) binds to a patient's HLA molecule (classically MHC class I or II). This complex is presented on the surface of cancer cells and is recognized by T-cell receptors (TCRs), enabling immune discrimination between healthy and malignant cells. These complexes are key targets for innovative cancer immunotherapies, including TCR-engineered T cells, TCR-mimic antibodies, and personalized neoantigen vaccines. Their specificity arises from their presentation of tumor-exclusive mutations not found in normal tissue, making them ideal for highly selective (but HLA- and mutation-restricted) therapy.

Other names

Mutant peptide–HLA complexNeoantigen–HLA complexTumor-specific peptide–MHC complexMutant peptide–major histocompatibility complex

Direct recognition by TCR (either endogenous or engineered) leads to targeted T-cell cytotoxicity against tumor cells displaying the mutant peptide–HLA complex. Monoclonal antibody binding to surface mutant peptide–HLA complex may lead to targeted killing or immune recruitment. Cancer vaccines elicit or enhance T-cell responses to these complexes.