Melanoma-associated antigen 3 (112–120) peptide presented by HLA-A*02:01 (MAGE-A3/HLA-A*02:01)

The MAGE-A3 112–120 peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for cancer immunotherapy. MAGE-A3 (Melanoma-associated antigen 3) is a member of the cancer-testis antigen family, which is typically expressed in various malignancies but not in normal adult tissues, except for the testis and placenta (UniProt P43357). The specific nonamer peptide KVAELVHFL (residues 112–120) is processed intracellularly and presented on the cell surface by the HLA-A*02:01 MHC class I molecule. This complex is targeted by engineered T-cell receptor (TCR) therapies, where a patient's T cells are modified to recognize this specific pMHC and eliminate tumor cells. However, clinical development has been hindered by significant safety concerns, most notably off-target cross-reactivity. High-profile clinical trials reported fatal toxicities when engineered TCRs recognized similar sequences in the cardiac protein Titin and the brain-expressed MAGE-A12 (Linette et al., 2013; Morgan et al., 2013). Consequently, this target remains a high-interest but high-risk focus for precision oncology, requiring rigorous validation of TCR specificity.

Other names

MAGE-A3 p112-120KVAELVHFL peptideMAGE-A3:112-120/HLA-A*02:01KVAELVHFL-HLA-A*02:01 complex

T-cell receptor (TCR) mediated T-cell activation and tumor cell lysis