Melanoma-associated antigen A4 (MAGE-A4) peptide 230-239 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 the immune-privileged germ cells of the testis and placenta but becomes aberrantly expressed in various solid tumors, including synovial sarcoma and non-small cell lung cancer [UniProt P43358]. The specific epitope consisting of amino acids 230-239 (GVYDGREHTV) is processed intracellularly and presented on the cell surface by the Human Leukocyte Antigen (HLA)-A*02 allele [PubMed: 32703754]. This peptide-MHC complex serves as a highly specific target for T-cell receptor (TCR)-based immunotherapies, as it is absent from most healthy adult tissues, thereby minimizing the risk of on-target, off-tumor toxicity [PubMed: 34291201]. Therapeutic strategies targeting this complex include engineered TCR-T cell therapies, such as afamitresgene autoleucel, which redirect a patient's T cells to recognize and eliminate MAGE-A4-expressing malignant cells [FDA, 2024]. Clinical efficacy has been demonstrated in patients with advanced synovial sarcoma, leading to the first regulatory approval for a TCR-T cell therapy in 2024 [FDA, 2024]. Monitoring for HLA-A*02:01 status and MAGE-A4 expression levels via immunohistochemistry is essential for patient selection and treatment success [NCT03139747].

Other names

MAGE-A4 p230-239GVYDGREHTV peptideMAGE-A4/HLA-A2 complexMAGE-A4(230-239)/HLA-A*02:01MAGE-A4 peptide presented by MHC class I

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and cytotoxic destruction of the target cell.