Melanoma-associated antigen 4 peptide–HLA-A*02:01 complex (MAGE-A4/HLA-A*02:01)

The MAGE-A4/HLA-A*02:01 complex is formed when an antigenic peptide derived from the MAGE-A4 protein—part of the cancer/testis antigen family—binds to the MHC class I molecule HLA-A*02:01 on tumor cells. MAGE-A4 is almost exclusively expressed in tumors (and not in healthy somatic tissues, except testis and placenta) and is implicated in apoptosis and cell cycle regulation. Presentation of MAGE-A4 peptides by HLA-A*02:01 enables cytotoxic T cells to specifically recognize and destroy cancer cells, making this complex a highly attractive target for immunotherapies such as engineered T cell therapies and bispecific antibodies. Drugs targeting this complex, such as afami-cel, have shown efficacy in selectively killing tumor cells in patients with the relevant HLA genotype and tumor antigen expression. Safety concerns include the risk of targeting normal tissues where MAGE-A4 is physiologically expressed and immune-related adverse effects. This target is commonly utilized for development of cancer immunotherapies, patient selection frequently involves testing for the presence of both MAGE-A4 expression in the tumor and HLA-A*02:01 in the patient genotype.

Other names

MAGEA4/HLA-A*02:01HLA-A2/MAGE-A4Melanoma antigen family A4–HLA-A*02:01MAGE4-HLA-A2 complex

T-cell mediated cytotoxicity: T cells recognize the peptide–MHC complex and kill tumor cells presenting the antigen; Bispecific antibody-mediated T cell recruitment and activation