Melanoma-associated antigen 1 peptide epitopes presented on MHC (MAGE-A1/MHC)

Melanoma-associated antigen 1 (MAGE-A1) peptide epitopes presented on MHC molecules are highly specific targets for cancer immunotherapy [3, 17]. MAGE-A1 is a cancer-testis antigen (CTA) that is normally expressed only in the testis, an immune-privileged site where MHC Class I molecules are absent [11, 17]. In many cancers, including melanoma, lung cancer, and hepatocellular carcinoma, MAGE-A1 is aberrantly re-expressed and its peptides are presented on the cell surface by MHC molecules, such as HLA-A*02:01, HLA-A*01:01, or HLA-C*07:02 [1, 10, 18]. Biologically, MAGE-A1 acts as a transcriptional corepressor and can inhibit p53-mediated apoptosis by blocking its interaction with chromatin, promoting tumor survival and progression [6, 17]. Because of its tumor-restricted presentation, it is a primary target for T-cell receptor-engineered T-cell (TCR-T) therapies like IMA202 and TK-8001, as well as therapeutic vaccines [1, 21, 24]. These treatments aim to leverage the immune system to recognize and destroy MAGE-A1-positive tumor cells while sparing healthy tissues [7, 15]. However, therapeutic efficacy can be limited by challenges such as cytokine release syndrome (CRS), neurotoxicity, and the loss of HLA expression by tumor cells [16, 21, 22].

Other names

MAGE-A1/HLA complexMAGE-A1 pMHCMZ2-E peptide/MHCMelanoma-associated antigen 1/MHC complexMAGE-A1 epitope

Targeting of peptide-MHC complexes by engineered T-cell receptors (TCR-T) or vaccines to induce cytotoxic T-lymphocyte-mediated tumor cell lysis.