Melanoma-associated antigen A4 peptide (230-239) presented by Human Leukocyte Antigen A*02:01 (MAGE-A4/HLA-A*02:01)

Melanoma-associated antigen A4 peptide (230-239) presented by Human Leukocyte Antigen A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target consisting of a 10-amino acid peptide (GVYDGREHTV) derived from the MAGE-A4 protein, presented on the cell surface by the HLA-A*02:01 molecule [3, 18]. MAGE-A4 is a cancer-testis antigen (CTA) that is highly expressed in various solid tumors—including synovial sarcoma, non-small cell lung cancer, and ovarian cancer—but is typically absent in normal adult tissues except for immune-privileged sites like the testis and placenta [9, 15]. This restricted expression pattern makes the MAGE-A4/HLA-A*02:01 complex an ideal target for precision immunotherapies, such as T-cell receptor (TCR) engineered T-cell therapies and TCR-based bispecific T-cell engagers [1, 11].\n\nIn August 2024, the FDA granted accelerated approval to afamitresgene autoleucel (Tecelra), the first TCR-T therapy targeting this complex, for the treatment of metastatic synovial sarcoma [2, 5]. Therapeutic engagement of this target triggers a potent cytotoxic T-cell response against tumor cells, though it requires patients to be both HLA-A*02:01 positive and have MAGE-A4-expressing tumors [7, 20]. Clinical challenges include managing cytokine release syndrome (CRS) and ensuring specificity to avoid off-target effects against related MAGE family proteins [5, 15].

Other names

MAGE-A4(230-239)/HLA-A*02:01MAGE-A4/HLA-A2GVYDGREHTV/HLA-A*02:01MAGE-A4 pMHC complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation and targeted lysis of MAGE-A4-expressing tumor cells.