Melanoma-associated antigen A4 peptide–Major Histocompatibility Complex class I (MAGE-A4–MHC complex)

Melanoma-associated antigen A4 (MAGE-A4) is a member of the cancer-testis antigen (CTA) family, characterized by high expression in various malignant tumors and restricted expression in healthy adult tissues, primarily the immune-privileged germ cells of the testes. The therapeutic target is a specific peptide fragment of the MAGE-A4 protein (most commonly the GVYDGREHTV decamer) presented on the tumor cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02. This peptide-MHC complex serves as a highly specific neoantigen-like target for the immune system. (UniProt P43358; PMID: 32603453). Therapeutic interventions targeting this complex include TCR-engineered T-cell therapies (TCR-T) and bispecific T-cell engagers, such as ImmTACs. These drugs are designed to bypass natural immune tolerance by providing high-affinity receptors that recognize the MAGE-A4/HLA complex, triggering a potent cytotoxic T-lymphocyte response against the tumor. The clinical significance of this target was recently validated by the FDA approval of afamitresgene autoleucel (Tecelra) for the treatment of advanced synovial sarcoma, marking it as a cornerstone of modern precision immunotherapy for solid tumors. (PMID: 34380005; FDA 2024).

Other names

MAGE-A4/HLA complexMAGE-A4 peptide-HLA-A*02 complexMelanoma-associated antigen 4 peptide-MHCMAGEA4-pMHC

T-cell receptor (TCR) mediated recognition of the specific MAGE-A4 peptide presented by HLA class I molecules, leading to T-cell activation and targeted lysis of tumor cells.