Melanoma-associated antigen 4 (MAGE-A4) peptide-HLA complex (MAGE-A4/HLA)

Melanoma-associated antigen 4 (MAGE-A4) is a member of the cancer-testis antigen (CTA) family, which is characterized by restricted expression in immune-privileged germ cells of the testis and placenta, but high expression in various malignant tissues (UniProt P43358). The therapeutic target consists of specific MAGE-A4-derived peptide epitopes, such as the HLA-A*02:01-restricted GVYDGREHTV sequence, which are processed intracellularly and presented on the cell surface by Human Leukocyte Antigen (HLA) complexes (PubMed: 30610146). This presentation makes the intracellular protein "visible" to the immune system, specifically to T-cells. In oncology, this complex is targeted by adoptive cell therapies, such as TCR-engineered T-cells (TCR-T), which are designed to bind the peptide-HLA complex with high affinity. The restricted expression profile of MAGE-A4 in healthy tissues minimizes the risk of on-target, off-tumor toxicity, making it a prominent target for treating solid tumors like synovial sarcoma and non-small cell lung cancer (FDA.gov, 2024). Recent clinical successes, including the approval of afamitresgene autoleucel, highlight its significance as a validated target in precision immunotherapy (PubMed: 34344820).

Other names

MAGE-A4Melanoma antigen family A member 4MAGE4Cancer/testis antigen 1.4CT1.4MAGE-X2

Engineered T-cell receptor (TCR) therapy designed to recognize and bind specifically to MAGE-A4 peptide fragments presented by HLA molecules, leading to T-cell activation and tumor cell lysis.