Melanoma-associated antigen 1 peptide presented by Human leukocyte antigen A2 (MAGE-A1/HLA-A2)

The MAGEA1-derived peptide presented by HLA-A2 is a specific peptide-major histocompatibility complex (pMHC) target utilized in cancer immunotherapy. MAGE-A1 (Melanoma-associated antigen 1) is a member of the cancer-testis antigen (CTA) family, which is typically expressed in various malignant tumors but restricted to immune-privileged tissues like the testes and placenta in healthy individuals (UniProt P43355). Since these normal tissues do not express HLA Class I molecules, the MAGE-A1 peptide-HLA-A2 complex serves as a highly tumor-specific target. The HLA-A2 allele, specifically HLA-A*02:01, is the most frequent MHC Class I molecule in many populations, facilitating the broad application of therapies targeting this complex. Current therapeutic approaches include T-cell receptor (TCR) engineered T-cells, such as TK-8001, which are designed to recognize the KVLEYVIKV peptide sequence within the HLA-A2 binding groove (PubMed 1565145, NCT04511871). Recognition of this complex by cytotoxic T lymphocytes triggers the release of perforins and granzymes, leading to the selective destruction of cancer cells. Clinical investigations are primarily focused on solid tumors, including melanoma and non-small cell lung cancer, where MAGE-A1 is frequently overexpressed. However, the development of these therapies requires rigorous screening to avoid cross-reactivity with similar peptides in vital organs, a challenge highlighted by previous MAGE-family clinical trials (PubMed 23908470).

Other names

MAGE-A1/HLA-A*02:01MAGE-A1 peptide-MHC complexAntigen MZ2-EKVLEYVIKV-HLA-A2 complexMAGE-1/HLA-A2

T-cell receptor (TCR) mediated recognition of the MAGE-A1 peptide/HLA-A2 complex, leading to the activation of cytotoxic T lymphocytes and subsequent lysis of tumor cells expressing the antigen.