Melanoma-associated antigen 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 (UniProt P43358). MAGE-A4 is a member of the cancer-testis antigen family, which is typically expressed only in immune-privileged germ cells of the testis but becomes aberrantly expressed in various solid tumors, including synovial sarcoma and non-small cell lung cancer (D'Angelo et al., The Lancet, 2024). Because the testis lacks HLA expression, the presentation of this peptide on tumor cells makes it a highly specific target for adoptive T-cell therapies with minimal risk of off-target toxicity in healthy somatic tissues. Therapeutic intervention involves T-cell receptor (TCR) engineered T-cells, such as afamitresgene autoleucel, which was the first TCR-T therapy to receive FDA approval for metastatic synovial sarcoma (FDA, 2024). This target is restricted to patients who are both HLA-A*02:01 positive and have tumors that demonstrate high MAGE-A4 expression via immunohistochemistry (Adaptimmune, 2024).

Other names

MAGE-A4 230-239 peptideMAGE-A4 pMHCGVYDGREHTV-HLA-A*02:01 complexMAGE-A4/HLA-A2Melanoma-associated antigen 4 peptide

Engineered T-cell receptor (TCR) therapy designed to recognize and bind the specific peptide-MHC complex, leading to T-cell activation and cytotoxic destruction of the target tumor cell.