Melanoma-associated antigen A4 peptide presented by Human Leukocyte Antigen A*24:02 (MAGE-A4/HLA-A*24:02)

The MAGE-A4 peptide presented by HLA-A*24:02 is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy [PMID: 31515463]. MAGE-A4 (Melanoma-associated antigen A4) is a member of the cancer-testis antigen family, which is highly expressed in various solid tumors—including synovial sarcoma, esophageal cancer, and non-small cell lung cancer—but is restricted to the immune-privileged testes and placenta in healthy tissues [PMID: 10446440]. The HLA-A*24:02 allele is a common MHC Class I molecule, particularly prevalent in East Asian populations, that presents specific MAGE-A4-derived peptides to the immune system [PMID: 15603406]. Therapeutic strategies targeting this complex primarily involve T-cell receptor (TCR) engineered T-cell therapies, where patient T cells are modified to express a TCR that specifically recognizes this pMHC [Takara Bio, 2023]. Upon binding, these engineered T cells initiate a potent cytotoxic response against MAGE-A4-positive tumor cells [Astellas, 2022]. This target is particularly valuable for precision oncology in patient populations carrying the HLA-A*24:02 allele, offering a tumor-specific approach with minimal impact on normal somatic tissues. Clinical candidates like TBI-1301 and ASP0739 are currently being evaluated for their efficacy in treating MAGE-A4-expressing cancers in HLA-A*24:02-positive patients [ClinicalTrials.gov, NCT02869217].

Other names

MAGE-A4/HLA-A*24:02 complexMAGE-A4 143-151/HLA-A*24:02MAGE-A4/HLA-A24MAGE-A4 peptide-MHC complex

Engineered T-cell receptors (TCRs) recognize the specific MAGE-A4 peptide epitope (typically NYKRCFPVI) bound within the groove of the HLA-A*24:02 molecule, facilitating the formation of an immunological synapse and triggering cytotoxic T-cell mediated lysis of the tumor cell [PMID: 31515463, PMID: 10446440].