Melanoma-associated antigen 1 peptide presented by Human Leukocyte Antigen A*02:01 or A*01:01 (MAGE-A1/HLA-A*02:01 or HLA-A*01:01)

Melanoma-associated antigen 1 (MAGE-A1) is a member of the cancer-testis antigen (CTA) family, characterized by its restricted expression in male germ cells and its aberrant expression in various human cancers (UniProt P43355). The MAGE-A1 peptide, when processed and presented on the cell surface by Human Leukocyte Antigen (HLA) alleles A*02:01 or A*01:01, forms a peptide-MHC (pMHC) complex that can be recognized by specific T-cell receptors (TCRs) (Traversari et al., 1992, PubMed: 1355644; Pascolo et al., 2001, PubMed: 11160694). This complex is a significant therapeutic target in oncology because its presence is highly tumor-specific, minimizing the risk of attacking healthy somatic tissues. Therapeutic strategies primarily involve TCR-engineered T-cell (TCR-T) therapies and bispecific molecules that redirect T-cells to kill MAGE-A1-positive tumor cells (ClinicalTrials.gov NCT04552223). Clinical development has focused on treating solid tumors such as melanoma and non-small cell lung cancer, where MAGE-A1 is frequently overexpressed. However, a critical challenge in targeting this complex is ensuring the TCR's specificity to avoid cross-reactivity with similar peptides found in vital organs, a lesson learned from previous MAGE-family clinical trials.

Other names

MAGE-1Melanoma antigen family A 1Cancer/testis antigen 1.1CT1.1MAGE-A1 pMHCMAGE-A1/HLA-A*02:01MAGE-A1/HLA-A*01:01

T-cell receptor engineered T-cell therapy (TCR-T) designed to recognize the specific MAGE-A1 peptide in the context of HLA-A*02:01 or HLA-A*01:01, leading to T-cell activation and tumor cell lysis.