Melanoma-associated antigen 6 (MAGE-A6) (MAGEA6)

Melanoma-associated antigen 6 (MAGE-A6) is a member of the Type I MAGE family, specifically classified as a cancer/testis antigen (CTA). In healthy tissues, its expression is restricted to the immune-privileged germ cells of the testis and placenta, which lack MHC class I expression (UniProt P43360). However, MAGE-A6 is frequently overexpressed in various malignancies, including melanoma and lung cancer, where it promotes oncogenesis by acting as a scaffold for the TRIM28 E3 ubiquitin ligase. This interaction leads to the degradation of the tumor suppressor AMPK, thereby activating the mTORC1 pathway and facilitating tumor cell survival and proliferation (Pineda et al., 2015). Because of its tumor-specific expression profile, MAGE-A6 is a prominent target for cancer immunotherapies, such as T-cell receptor (TCR) engineered T-cell therapies and cancer vaccines (NIH). These therapies aim to induce a robust cytotoxic T-lymphocyte response against tumor cells presenting MAGE-A6-derived peptides. Current clinical research focuses on optimizing target specificity to avoid cross-reactivity with other closely related MAGE proteins.

Other names

MAGE6MAGE-6 antigenCancer/testis antigen 1.6CT1.6

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) response against tumor cells expressing MAGE-A6 peptides presented on MHC molecules, or inhibition of its oncogenic E3 ligase scaffolding function.