Melanoma-associated antigen 6 (MAGE-A6) peptide-MHC complex (MAGE-A6 pMHC)

Melanoma-associated antigen 6 (MAGE-A6) is a member of the cancer-testis antigen (CTA) family, characterized by its restricted expression in the immune-privileged tissues of the testis and placenta and its aberrant expression in various solid tumors (UniProt P43360). Peptides derived from MAGE-A6 are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, such as HLA-A*02:01, forming a peptide-MHC (pMHC) complex (PMID: 23620577). This pMHC complex serves as a highly specific target for T-cell receptors (TCRs), making it a prime candidate for adoptive T-cell therapies (TCR-T) and cancer vaccines (PMID: 30104343). Clinical candidates like IMA202 and KITE-718 have been developed to target the MAGE-A3/A6 pMHC complex, demonstrating the target's relevance in treating melanoma and lung cancer (ClinicalTrials.gov NCT03441100). However, the high sequence homology between MAGE-A6 and other MAGE-A family members, particularly MAGE-A12, presents a significant risk of off-target cross-reactivity and associated toxicities (PMID: 23908471).

Other names

MAGEA6Melanoma antigen family A 6Cancer/testis antigen 1.6CT1.6MAGE-A6 antigenMAGE-A6-derived peptide

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