Melanoma-associated antigen 4 peptide–HLA-A*2402 complex (MAGE-A4/HLA-A*2402)

The MAGE-A4 peptide–HLA-A*2402 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for cancer immunotherapy. MAGE-A4 (Melanoma-associated antigen 4) is a member of the cancer-testis antigen family, which is typically expressed only in germ cells of the testis and placenta but is aberrantly overexpressed in various solid tumors, including synovial sarcoma and non-small cell lung cancer (Source: UniProt P43358; PubMed: 30635454). In patients carrying the HLA-A*2402 allele, a specific peptide fragment of the MAGE-A4 protein is processed and presented on the cell surface by the HLA molecule (Source: Allele Frequency Net Database). This complex is recognized by specific T-cell receptors (TCRs), making it a viable target for TCR-engineered T-cell (TCR-T) therapies, such as TBI-1601 (Source: Takara Bio; ClinicalTrials.gov NCT04729543). Because MAGE-A4 expression is highly restricted in healthy adult tissues, targeting this complex minimizes the risk of on-target, off-tumor toxicity. Clinical development focuses on patients who are both MAGE-A4 positive by immunohistochemistry and HLA-A*2402 positive by genetic testing.

Other names

MAGE-A4/HLA-A*24:02MAGE-A4/A24MAGE4-HLA-A24 complexMAGE-A4 peptide-MHC complex

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity