Melanoma-associated antigen 4 peptide–Major histocompatibility complex (MAGE-A4/MHC)

The Melanoma-associated antigen 4 (MAGE-A4) peptide–Major histocompatibility complex (MHC) is a highly specific tumor target composed of a processed MAGE-A4 peptide fragment presented by Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01 (UniProt P43358). MAGE-A4 is a member of the cancer-testis antigen (CTA) family, which is characterized by restricted expression in the testes and placenta of healthy individuals but high expression in various malignancies, including synovial sarcoma, myxoid/round cell liposarcoma, and non-small cell lung cancer (PubMed 32718245). This restricted expression pattern makes the MAGE-A4/MHC complex an ideal target for immunotherapy, as it minimizes the risk of off-target toxicity in normal tissues. Therapeutic interventions primarily involve engineered T-cell receptor (TCR) therapies, such as the FDA-approved afamitresgene autoleucel, which are designed to recognize and bind this complex with high affinity (FDA 2024). Upon binding, the engineered T-cells undergo activation and expansion, leading to the secretion of cytotoxic proteins like perforin and granzymes that induce apoptosis in the target tumor cells. This mechanism provides a potent and targeted approach for treating solid tumors that have historically been resistant to conventional therapies.

Other names

MAGE-A4/HLA complexMAGE-A4/HLA-A*02:01Melanoma antigen family A 4 peptide-MHCMAGE-A4 peptide-MHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation, cytokine release, and cytotoxic lysis of tumor cells (PubMed 32718245).