Melanoma-associated antigen A4 peptide–MHC class I complex (MAGE-A4 pMHC)

The Melanoma-associated antigen A4 (MAGE-A4) peptide–MHC class I complex is a specific molecular target found on the surface of various malignant cells. MAGE-A4 is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in immune-privileged sites like the testis and placenta but becomes aberrantly re-expressed in numerous solid tumors, including synovial sarcoma and non-small cell lung cancer (Frontiers in Oncology, 2024; Cancer Treatment Reviews, 2025). Within the tumor cell, MAGE-A4 proteins are processed into short peptide fragments, such as the 230-239 epitope, which are then loaded onto MHC class I molecules (primarily HLA-A*02) and transported to the cell surface (Frontiers in Oncology, 2024; NIH, 2025). This complex acts as a flag for the immune system, specifically for T cells equipped with high-affinity T-cell receptors (TCRs) designed to recognize this unique peptide-HLA combination (BMJ Open, 2022; Synovial Sarcoma Foundation, 2026). Drugs targeting this complex, such as the FDA-approved afamitresgene autoleucel, leverage this recognition to induce potent, tumor-specific cytolytic activity (OncLive, 2024; Tecelra Prescribing Information, 2024). Because MAGE-A4 is not expressed in most healthy adult tissues, targeting this complex offers a high degree of therapeutic selectivity, although challenges such as cytokine release syndrome and potential MHC downregulation remain significant considerations (Tecelra Prescribing Information, 2024; Synovial Sarcoma Foundation, 2026).

Other names

MAGE-A4/HLA-A*02 complexMAGE-A4 peptide-HLA complexMAGE-A4 p230-239/HLA-A*02:01 complexMAGE-A4 pMHCMAGE-A4 peptide–MHC class I complex on tumor cells

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and tumor cell lysis.