Melanoma-associated antigen A4 (MAGE-A4) peptide GVYDGREHTV presented by HLA-A*02 (MAGE-A4/HLA-A*02)

Melanoma-associated antigen A4 (MAGE-A4) is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in immune-privileged germ cells of the testis but is aberrantly overexpressed in various solid tumors, including synovial sarcoma and non-small cell lung cancer (UniProt P43358). The specific decamer peptide GVYDGREHTV, corresponding to residues 230-239 of the MAGE-A4 protein, is processed intracellularly and presented on the cell surface by the Human Leukocyte Antigen (HLA)-A*02:01 molecule (PubMed: 32814720). This peptide-MHC (pMHC) complex serves as a highly specific target for T-cell receptor (TCR) engineered therapies, which are designed to recognize the complex and induce T-cell mediated lysis of cancer cells (Nature Medicine, 2019). Afamitresgene autoleucel (Tecelra) is the first FDA-approved TCR-T cell therapy targeting this specific pMHC complex for patients with advanced synovial sarcoma (FDA.gov, 2024). Other investigational agents, such as the bispecific ImmTAC IMC-C103C, also target this complex to recruit and activate T-cells within the tumor microenvironment (Immunocore, 2023). Because MAGE-A4 is not expressed in vital healthy tissues, it represents a promising target for minimizing off-tumor toxicity while achieving high tumor specificity.

Other names

MAGE-A4 230-239 peptide-HLA-A*02 complexMAGE-A4 pMHCMAGEA4-HLA-A2GVYDGREHTV-HLA-A*02:01MAGE-A4 antigen

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