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

Melanoma-associated antigen A4 (MAGE-A4) is a member of the cancer-testis antigen (CTA) family, which is typically restricted to the germ cells of the testis but is aberrantly expressed in various malignancies such as synovial sarcoma and non-small cell lung cancer (UniProt P43358; PubMed: 32603455). The therapeutic target is the specific MAGE-A4 peptide (most commonly the GVYDGREHTV decamer) presented by Human Leukocyte Antigen (HLA) class I molecules, primarily HLA-A*02, on the surface of tumor cells (PubMed: 30104351). This peptide-HLA complex serves as a highly specific marker, allowing the immune system to recognize intracellular oncogenic proteins that are otherwise inaccessible to standard antibody therapies. Therapeutic interventions, such as the FDA-approved afamitresgene autoleucel (Tecelra), employ T-cell receptor (TCR) engineered T-cells to bind this complex and trigger a potent cytotoxic immune response (FDA.gov, 2024). Because MAGE-A4 is not expressed in healthy somatic tissues, this target offers a wide therapeutic window, although clinicians must monitor for cytokine release syndrome (CRS) and potential off-target reactivity (PubMed: 34155012).

Other names

MAGE-A4Melanoma antigen family A 4Cancer/testis antigen 1.4CT1.4MAGEA4

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