Melanoma-associated antigen 6 peptide presented by Human leukocyte antigen A*02:01 (MAGE-A6/HLA-A*02:01)

Melanoma-associated antigen 6 (MAGE-A6) is a member of the Type I Cancer-Testis Antigen (CTA) family, which is characterized by high expression in various malignancies and restricted expression in normal adult tissues, primarily the immune-privileged testis and placenta (nih.gov, maayanlab.cloud). When processed intracellularly, MAGE-A6 proteins are cleaved into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, such as the common HLA-A*02:01 allele (nih.gov). This peptide-MHC (pMHC) complex serves as a highly specific target for the immune system, particularly for T-cell receptor (TCR) engineered T-cell therapies (frontiersin.org). Biologically, MAGE-A6 acts as a co-factor for E3 ubiquitin ligases like TRIM28, facilitating the degradation of tumor suppressors such as p53 and AMPK, thereby promoting tumor cell survival, proliferation, and the inhibition of autophagy (elifesciences.org, nih.gov). In the context of drug development, the MAGE-A6/HLA-A*02:01 complex is targeted by adoptive cell therapies, most notably TCR-T cells like KITE-718, which are designed to recognize and eliminate tumor cells expressing these antigens (cancer.gov, patsnap.com). However, therapeutic targeting of the MAGE family faces significant challenges, including the risk of off-target toxicity due to high sequence homology between MAGE family members and potential cross-reactivity with proteins in healthy tissues, such as Titin in the heart or MAGE-A12 in the brain (frontiersin.org, nih.gov). Clinical monitoring for these therapies typically involves screening patients for the HLA-A*02:01 genotype and verifying MAGE-A6 expression in tumor biopsies (nih.gov).

Other names

MAGEA6-HLA-A*02:01 complexMAGE-A6 pMHCMelanoma antigen family A 6 peptide-MHC complexMAGE-A6/HLA-A2

T-cell receptor-engineered T-cell (TCR-T) therapy