Melanoma-associated antigen 3 (MAGE-A3) peptide epitope presented by HLA-A*01 (MAGE-A3/HLA-A1 complex)

The MAGE-3A1 peptide epitope refers to a specific amino acid sequence (typically EVDPIGHLY) derived from the Melanoma-associated antigen 3 (MAGE-A3) protein, processed and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele HLA-A*01:01. MAGE-A3 is a prominent member of the cancer-testis antigen (CTA) family, meaning it is highly expressed in various malignancies—including melanoma, lung, and bladder cancers—but is restricted to immune-privileged sites like the testes and placenta in healthy adults (UniProt P43357). This restricted expression pattern makes the MAGE-A3/HLA-A1 complex an ideal target for TCR-engineered T-cell therapies and therapeutic vaccines designed to trigger a CD8+ cytotoxic T-lymphocyte response against tumor cells (PubMed: 23913172). However, clinical development has faced significant challenges due to off-target cross-reactivity; notably, early TCR-T trials resulted in fatal cardiac toxicity because the engineered receptors mistakenly recognized a similar peptide from the muscle protein Titin (PubMed: 23761451). Current research focuses on improving the specificity of TCRs and bispecific molecules to safely exploit this target for immunotherapy (PubMed: 32661138).

Other names

MAGE-3MAGEA3Antigen MZ2-DCancer/testis antigen 1.3EVDPIGHLY peptideMAGE-A3/HLA-A*01:01

T-cell receptor (TCR) binding, T-cell mediated cytotoxicity, Vaccine-induced active immunization