Melanoma-associated antigen A2 (MAGE-A2) peptide presented by Human leukocyte antigen A*01:01 (HLA-A*01:01) (MAGE-A2/HLA-A*01:01)

The MAGE-A2 peptide presented by HLA-A*01:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a potent target for cancer immunotherapy. MAGE-A2 is a member of the Type I Cancer-Testis Antigen (CTA) family, which is characterized by high expression in various malignant tumors but restricted expression in normal adult tissues, primarily the testis and placenta [1, 2]. The specific nonapeptide sequence, often EVDPIGHLY, is processed intracellularly and loaded onto the HLA-A*01:01 molecule for presentation on the cell surface to CD8+ cytotoxic T lymphocytes [3]. Because this peptide sequence is shared among MAGE-A2, MAGE-A3, and MAGE-A6, therapies targeting this complex often exhibit multi-antigen specificity. Therapeutic approaches include the development of T-cell receptor (TCR) engineered T-cells and bispecific molecules designed to redirect the immune system to eliminate MAGE-expressing cancer cells [5]. However, clinical development has been complicated by significant safety hurdles, most notably a high-profile instance of lethal cardiotoxicity caused by TCR cross-reactivity with a similar peptide in the cardiac protein Titin [4]. Despite these challenges, the target remains highly attractive due to its tumor-specific expression profile and the prevalence of the HLA-A*01:01 allele in the patient population.

Other names

MAGE-A2/HLA-A1 complexMAGEA2-HLA-A*01:01EVDPIGHLY-HLA-A*01:01 complexMAGE-A2 peptide-MHC complex

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