Melanoma-associated antigen (MAGE) (MAGE)

Melanoma-associated antigens (MAGE) are a large family of proteins, primarily the Type I MAGE-A subfamily, that serve as significant targets in cancer immunotherapy [1, 4]. Originally discovered in melanoma, these proteins are classified as cancer-testis antigens (CTAs) because they are typically expressed only in the immune-privileged germ cells of the testis and placenta but are aberrantly re-expressed in a wide variety of malignant tumors [7, 8]. In cancer cells, MAGE proteins often function as regulatory subunits for E3 ubiquitin ligases, such as TRIM28, facilitating the degradation of tumor suppressors like p53 and promoting cell survival, proliferation, and resistance to apoptosis [3, 5, 13]. Due to their highly tumor-specific expression profile, MAGE-A antigens (notably MAGE-A3 and MAGE-A4) are ideal candidates for targeted therapies, including cancer vaccines and adoptive T-cell therapies [1, 6]. For instance, afamitresgene autoleucel is an FDA-approved TCR-T therapy that targets MAGE-A4 in synovial sarcoma [14]. However, the development of MAGE-targeted therapies faces challenges, such as the risk of off-target cross-reactivity with similar proteins in normal tissues, which has historically led to severe adverse events in clinical trials [14, 20].

Other names

MAGE familyCancer/testis antigen (CTA)Melanoma antigenMAGE-A subfamilyType I MAGE

T-cell receptor (TCR) engineered T-cell therapy, Cancer vaccination (peptide/mRNA), Epigenetic induction of antigen expression