Melanoma-associated antigen A4 (MAGE-A4) peptide GVYDGREHTV presented by HLA-A*02:01 (MAGE-A4/HLA-A*02:01)

The target is a specific peptide-major histocompatibility complex (pMHC) consisting of the GVYDGREHTV peptide (residues 230-239) derived from the Melanoma-associated antigen A4 (MAGE-A4) protein, presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01 (D'Angelo et al., 2024, The Lancet; UniProt P43358). MAGE-A4 is a member of the cancer-testis antigen (CTA) family, which is characterized by high expression in various malignant tumors but restricted expression in normal tissues, primarily the immune-privileged site of the testis (Sanderson et al., 2020, JITC). This restricted expression pattern makes the MAGE-A4/HLA-A*02:01 complex a highly specific target for immunotherapy, minimizing the risk of off-tumor toxicity in healthy tissues (Hong et al., 2023, JCO). Therapeutic intervention typically involves adoptive T-cell therapy using autologous T cells engineered with a high-affinity T-cell receptor (TCR) designed to recognize this specific pMHC (FDA, 2024, "FDA approves first gene therapy to treat adults with metastatic synovial sarcoma"). Upon recognition, these engineered T cells, such as afamitresgene autoleucel, trigger a potent cytotoxic immune response, leading to the lysis of tumor cells and the release of pro-inflammatory cytokines (Adaptimmune Therapeutics, 2024). This target has gained significant clinical prominence following the regulatory approval of TCR-T therapies for advanced synovial sarcoma and myxoid/round cell liposarcoma (D'Angelo et al., 2024, The Lancet).

Other names

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

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