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

The melanoma-associated antigen A4 peptide presented on HLA-A*02:01 is a cancer/testis antigen-derived peptide (most commonly the GVYDGREHTV sequence from MAGE-A4) bound to the MHC class I molecule HLA-A*02:01 on the surface of tumor cells. This peptide-MHC complex forms a unique epitope recognized by high-affinity engineered T cell receptors or chimeric antigen receptors, allowing targeted immunotherapy of MAGE-A4–expressing cancers. Because MAGE-A4 expression in normal tissues is restricted to immune-privileged sites, its presentation by HLA-A*02:01 on tumor cells makes it an attractive target for solid tumor immunotherapy, now validated in multiple cancer types and by the FDA approval of afami-cel in synovial sarcoma and myxoid/round cell liposarcoma. Patient selection requires both tumor antigen positivity and the correct HLA genotype.

Other names

MAGE-A4 peptide/HLA-A*02:01 complexMAGE-A4/HLA-A2 complexMAGE-A4–derived epitope presented by HLA-A*02:01

TCR T cell therapy: high-affinity T cell receptor recognizes MAGE-A4 peptide presented on HLA-A*02:01, resulting in T cell activation, tumor cell lysis, and anti-tumor immune response CAR-T therapy: chimeric antigen receptor engineered to bind the MAGE-A4 peptide/HLA-A*02:01 complex, triggering cytotoxicity against cancer cells