Melanoma-associated antigen A4 peptide–Major Histocompatibility Complex (MAGE-A4–MHC)

The MAGE-A4 peptide–MHC complex is a therapeutic target consisting of a specific peptide fragment (typically GVYDGREHTV) derived from the Melanoma-associated antigen A4 (MAGE-A4) protein, presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, most commonly HLA-A*02:01 (UniProt P43358; FDA, 2024). MAGE-A4 belongs to the cancer-testis antigen family, which is characterized by high expression in various solid tumors—including synovial sarcoma, non-small cell lung cancer, and ovarian cancer—while remaining absent from healthy adult tissues except for the immune-privileged testes (PubMed: 32853475). This differential expression makes the complex a highly specific target for immunotherapy, minimizing the risk of systemic toxicity. Current therapeutic approaches primarily utilize adoptive cell transfer of autologous T-cells engineered with a high-affinity T-cell receptor (TCR) designed to recognize this specific peptide-MHC ligand. Upon recognition, these TCR-T cells, such as the FDA-approved afamitresgene autoleucel, initiate a potent cytotoxic immune response against the tumor cells (Nature Medicine, 2024). Clinical success is dependent on both the patient's HLA genotype and the level of MAGE-A4 expression within the tumor microenvironment.

Other names

MAGE-A4–HLA-A*02 complexMAGEA4-MHCHLA-A*02:01–MAGE-A4 peptide complexMAGE-A4–HLA-A2MAGE-A4 peptide–MHC complexes on antigen-presenting/tumor cells

Engineered T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity