Melanoma-associated antigen 12 peptide presented by Human Leukocyte Antigen A*01:01 (MAGE-A12/HLA-A*01:01)

MAGE-A12 (Melanoma-associated antigen 12) is a member of the Type I Cancer-Testis Antigen (CTA) family, which are proteins typically expressed during fetal development and in the adult testis but aberrantly re-expressed in various malignancies (UniProt P43366). The target complex consists of a specific MAGE-A12-derived peptide, often the EVDPIGHLY sequence, presented on the cell surface by the Human Leukocyte Antigen (HLA) A*01:01 molecule (Morgan et al., 2013, JCO). This peptide-MHC complex is a primary focus for adoptive T-cell therapies, specifically TCR-engineered T cells (TCR-T), designed to recognize and eliminate tumor cells (Adaptimmune). While CTAs were historically considered ideal tumor-specific targets, clinical investigations revealed that MAGE-A12 is expressed at low levels in the human brain, specifically within the grey matter and neurons (PubMed: 23547081). This expression led to severe, fatal inflammatory encephalopathy in patients treated with TCRs that recognized this complex, highlighting a significant on-target, off-tumor safety risk (National Cancer Institute). Consequently, therapeutic development targeting MAGE-A12/HLA-A*01:01 requires extreme precision and rigorous screening to avoid central nervous system toxicity.

Other names

MAGEA12-HLA-A*01:01MAGE-A12:A*01:01 complexMAGE-A12 peptide-MHC complexMAGE-A12:HLA-A1

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation, cytokine release, and granzyme/perforin-mediated lysis of the target cell.