Melanoma-associated antigen C2 peptide–major histocompatibility complex (MAGE-C2 peptide–MHC)

The Melanoma-associated antigen C2 (MAGE-C2) peptide–major histocompatibility complex (MHC) is a highly specific immunotherapy target consisting of a processed peptide fragment from the MAGE-C2 protein presented on the cell surface by MHC Class I molecules, most commonly HLA-A*02 (UniProt P43367; Immatics, 2024). MAGE-C2 belongs to the cancer-testis antigen (CTA) family, characterized by expression restricted to the immune-privileged germ cells of the testis in healthy adults and aberrant upregulation in various malignancies, including melanoma and prostate cancer (Gnjatic et al., 2010). Because the testis lacks MHC Class I expression, the MAGE-C2 peptide–MHC complex is not presented on normal tissues, making it an ideal target for minimizing on-target, off-tumor toxicity. Therapeutic strategies targeting this complex primarily utilize T-cell receptor (TCR) engineered T-cells or TCR-bispecific molecules designed to recognize the specific peptide-HLA configuration with high affinity (Immatics, 2024). These therapies, such as the IMA204 program, aim to trigger a potent cytotoxic T-lymphocyte response against cancer cells expressing the antigen (PubMed: 21695118). Clinical development focuses on leveraging this specificity to treat solid tumors that are often resistant to conventional checkpoint inhibitors.

Other names

MAGE-C2/HLA complexMAGE-C2/MHC class I complexCT10 peptide-MHCMAGE-C2/HLA-A*02 complexCancer/testis antigen 10 peptide-MHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and directed lysis of tumor cells.