Melanoma-associated antigen C2 (MAGE-C2) peptide-MHC complex (MAGE-C2/MHC)

Melanoma-associated antigen C2 (MAGE-C2) peptide-MHC complexes on plasmacytoid dendritic cells (pDCs) represent a specialized target in cancer immunotherapy, particularly for priming the immune system against tumors. MAGE-C2 is a member of the cancer-testis antigen family, which is characterized by restricted expression in the testis and high expression in various malignancies like melanoma and prostate cancer (UniProt Q9UBF1). When these peptides are presented by MHC class I molecules on pDCs, they serve as potent activators of antigen-specific CD8+ T cells, leveraging the pDC's unique ability to produce Type I interferons and facilitate cross-presentation (PubMed 24161174, 25607114). Therapeutic strategies targeting this complex include the use of pDC-based vaccines to induce anti-tumor immunity and the development of T-cell receptor (TCR) engineered T-cell therapies, such as MDG1011, which recognize the complex on the surface of cancer cells (Medigene AG). Because MAGE-C2 is not expressed in normal somatic tissues, it is considered a highly specific target with a low risk of off-target toxicity. However, the efficacy of targeting these complexes can be limited by tumor-mediated immune suppression or the loss of MHC expression on the tumor surface.

Other names

MAGE-C2-derived peptide–MHC complexes on plasmacytoid dendritic cellsCT10/MHC complexCancer/testis antigen 10 peptide-MHC complexMAGE-C2/HLA-A2 complexMAGE-C2/HLA-A*02:01 complex

T-cell receptor (TCR) recognition of the peptide-MHC complex on the cell surface, leading to the activation of cytotoxic T lymphocytes and subsequent lysis of MAGE-C2-expressing tumor cells.