Melanoma-associated antigen 6 peptide presented by Human Leukocyte Antigen A*01:01 (MAGE-A6/HLA-A*01:01)

The MAGE-A6 peptide presented by HLA-A*01:01 is a peptide-major histocompatibility complex (pMHC) that serves as a highly specific target for cancer immunotherapy. MAGE-A6 (Melanoma-associated antigen 6) is a member of the Cancer-Testis Antigen (CTA) family, which is characterized by restricted expression in immune-privileged germline tissues and high expression in various cancers, including melanoma and non-small cell lung cancer. The specific 9-mer peptide EVDPIGHVY is derived from MAGE-A6 and presented on the cell surface by the HLA-A*01:01 allele, allowing it to be recognized by engineered T-cell receptors (TCRs). Therapeutic approaches targeting this complex, such as the TCR-T therapy KITE-718, aim to leverage the immune system to selectively destroy tumor cells while sparing healthy tissues. However, a significant challenge in targeting this complex is the high sequence similarity between MAGE-A6 and other MAGE family members, as well as potential cross-reactivity with unrelated proteins like cardiac Titin, which has historically led to severe safety concerns in clinical trials.

Other names

MAGE-A6/A*01:01MAGEA6-HLA-A1 complexEVDPIGHVY/HLA-A*01:01Melanoma-associated antigen 6 peptide-MHC complex

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