Melanoma-associated antigen 3 peptide presented by HLA-A*02:01 (MAGE-A3/HLA-A*02:01)

Melanoma-associated antigen 3 (MAGE-A3) peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various malignant cells (UniProt, 2024). MAGE-A3 belongs to the cancer-testis antigen family, characterized by high expression in tumors and restricted expression in normal, immune-privileged tissues like the testis and placenta (Scanlan et al., 2004). This restricted expression pattern makes the MAGE-A3/HLA-A*02:01 complex an ideal target for T-cell-based immunotherapies, such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers (Immatics, 2023). These therapies are designed to recognize the intracellularly derived peptide fragment when displayed by the HLA-A*02:01 molecule, triggering a potent cytotoxic immune response against the tumor (Gilead/Kite, 2022). Clinical development has highlighted the importance of target specificity, as early trials encountered severe adverse events due to cross-reactivity with similar proteins in healthy tissues, such as MAGE-A12 in the brain (Morgan et al., 2013). Consequently, patient selection requires screening for both the HLA-A*02:01 allele and high MAGE-A3 expression levels in the tumor to ensure therapeutic efficacy and safety (Immatics, 2023).

Other names

MAGE-A3/HLA-A*02:01 complexMAGE-A3:HLA-A*02:01MAGEA3-001 peptide-MHCFLWGPRALV:HLA-A*02:01

T-cell receptor (TCR) binding to the peptide-MHC complex, inducing T-cell activation, cytokine release, and granzyme/perforin-mediated apoptosis of the target tumor cell.