Melanoma antigen A4 (MAGE-A4)

Melanoma antigen A4 (MAGE-A4) is a member of the MAGE-A subfamily of cancer-testis antigens (CTAs). Under physiological conditions, its expression is strictly limited to immune-privileged germ cells in the testis and placenta, but it is aberrantly re-expressed in a wide variety of solid tumors, including synovial sarcoma and non-small cell lung cancer (UniProt P43358; PMID: 31530558). Biologically, MAGE-A4 functions as a scaffold for E3 ubiquitin ligases, influencing protein stability and promoting oncogenic pathways such as cell cycle progression and the inhibition of apoptosis (PMID: 32814573). Because of its high tumor specificity and lack of expression in vital adult tissues, MAGE-A4 has become a premier target for adoptive T-cell therapies. Specifically, engineered T-cell receptor (TCR-T) therapies, such as afamitresgene autoleucel, are designed to recognize MAGE-A4 peptides presented by HLA-A*02 molecules on the surface of cancer cells, leading to targeted tumor lysis (PMID: 38537575).

Other names

MAGE4MAGE-41MAGE-X2CT1.4Cancer/testis antigen 1.4

T-cell receptor (TCR) engineered T-cell therapy designed to recognize and kill tumor cells presenting MAGE-A4 peptide fragments in the context of HLA-A*02.