Melanoma-associated antigen 3-derived HLA-A*02:01-restricted epitope (MAGE-A3/HLA-A2 epitope)

The MAGEA3-derived HLA-A2-restricted epitope is a specific peptide fragment, most commonly the decamer FLWGPRALV (residues 271-279), derived from the Melanoma-associated antigen 3 (MAGE-A3) and presented on the cell surface by the Human Leukocyte Antigen A*02:01 (HLA-A2) molecule (UniProt P43357; PubMed 8144866). MAGE-A3 is a member of the cancer-testis antigen family, which is characterized by high expression in various malignancies—including melanoma and non-small cell lung cancer—while remaining silent in healthy adult tissues except for the immune-privileged testes (PubMed 25971939). This highly restricted expression pattern makes the MAGE-A3/HLA-A2 complex an ideal target for precision cancer immunotherapies, such as T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers like ImmTACs (e.g., IMC-C103C) (PubMed 32433714). These therapies are designed to recognize the specific peptide-MHC complex with high affinity to trigger a potent cytotoxic T-lymphocyte response against tumor cells. However, a significant challenge in targeting this epitope is the potential for off-target toxicity, as the high similarity between MAGE family members or unrelated self-proteins can lead to lethal cross-reactivity, necessitating rigorous preclinical screening (PubMed 23733882).

Other names

MAGE-A3 peptide-HLA-A2 complexFLWGPRALVMAGEA3 271-279MAGE-A3/HLA-A*02:01MAGE-A3 antigenKVAELVHFLMAGEA3 112-120

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or bispecific T-cell engagers to induce cytotoxic T-lymphocyte mediated lysis of tumor cells.