Melanoma-associated antigen 1 (MAGE-A1) peptide-HLA complex (MAGE-A1/HLA complex)

Melanoma-associated antigen 1 (MAGE-A1) is a member of the cancer-testis antigen (CTA) family, characterized by its expression in various malignancies but restricted expression in normal tissues, primarily the testis and placenta (UniProt P43355). Because these normal tissues lack MHC Class I expression, MAGE-A1 is considered a highly specific target for cancer immunotherapy (PubMed: 1840448). The target consists of specific MAGE-A1-derived peptides, such as the HLA-A*01:01-restricted EADPTGHSY or the HLA-A*02:01-restricted KVLEYVIKV, presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (PubMed: 10438933). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells and TCR-like antibodies, which recognize the peptide-MHC complex to induce tumor cell lysis. Clinical development, such as with the TCR-T therapy GSK3845097, has focused on treating solid tumors like melanoma and non-small cell lung cancer (ClinicalTrials.gov: NCT04552743). The primary challenge in targeting this complex is ensuring high specificity to avoid cross-reactivity with other MAGE family members or unrelated self-peptides in vital organs.

Other names

MAGE-1Melanoma antigen family A 1Cancer/testis antigen 1.1CT1.1MAGEA1Antigen MZ2-E

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and tumor cell lysis.