HLA-A*02:01-restricted Melanoma-associated antigen A4 (MAGE-A4) peptide-MHC complex (HLA-A*02:01/MAGE-A4)

The HLA-A*02:01-restricted Melanoma-associated antigen A4 (MAGE-A4) peptide-MHC complex is a specific molecular target found on the surface of various malignant cells (Sanderson et al., 2020). MAGE-A4 is a cancer-testis antigen that is typically expressed during embryogenesis and in the germ cells of the testis but is aberrantly overexpressed in numerous solid tumors, including synovial sarcoma and non-small cell lung cancer (PubMed: 32690475). Because its expression in normal tissues is limited to immune-privileged sites, it serves as an ideal target for immunotherapy. The complex consists of a specific peptide derived from the MAGE-A4 protein presented by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule. Therapeutic approaches, such as TSC-202 TCR-T cells, utilize engineered T-cell receptors to specifically recognize and bind to this pMHC complex (TScan Therapeutics, 2023). Upon binding, the TCR-T cells are activated to release cytotoxic granules and cytokines, resulting in the targeted destruction of the tumor cells (Adaptimmune Therapeutics, 2024). This target is currently the focus of several clinical trials aiming to treat advanced solid tumors in patients who are HLA-A*02:01 positive and have MAGE-A4-expressing tumors.

Other names

MAGE-A4/HLA-A*02:01 complexMAGE-A4 peptide-HLA-A*02:01MAGE-A4 pMHCMelanoma-associated antigen A4 presented by HLA-A*02:01

T-cell receptor engineered T-cell (TCR-T) therapy involving the recognition of the specific MAGE-A4 peptide presented by the HLA-A*02:01 molecule on the surface of tumor cells, leading to T-cell activation and tumor cell lysis.