Melanoma-associated antigen A4 (MAGE-A4) peptide-HLA class I complex (MAGE-A4/HLA complex)

Melanoma-associated antigen A4 (MAGE-A4) peptide-HLA class I complex is a tumor-specific antigen target used in advanced immunotherapy (PMID: 32703754). MAGE-A4 belongs to the cancer-testis antigen (CTA) family, which is typically expressed in immune-privileged germ cells of the testis but is frequently overexpressed in various solid tumors, including synovial sarcoma and lung cancer (UniProt P43358). The target consists of a specific intracellularly processed MAGE-A4 peptide (commonly the GVYDGREHTV decamer) presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, most notably HLA-A*02:01 (PMID: 31142651). Because this complex is absent from healthy somatic tissues, it provides a high degree of tumor specificity for T-cell receptor (TCR) engineered therapies. Therapeutic agents like afamitresgene autoleucel utilize modified TCRs to recognize this pMHC complex, triggering a potent cytotoxic immune response against malignant cells (FDA, 2024). This target is particularly significant in the treatment of HLA-matched patients with MAGE-A4-positive unresectable or metastatic sarcomas (NCT03139747). Clinical development also extends to non-small cell lung cancer and head and neck cancers where MAGE-A4 expression is prevalent (PMID: 37333238).

Other names

MAGE-A4 peptide-MHC complexMAGE-A4/HLA-A*02:01 complexMAGEA4-HLA-A2MAGE-A4 pMHC

Engineered T-cell receptors (TCRs) or bispecific molecules bind specifically to the MAGE-A4 peptide presented by HLA class I molecules, leading to T-cell activation and targeted lysis of tumor cells (PMID: 32703754).