Melanoma-associated antigen C2 (MAGE-C2) (MAGE-C2)

Melanoma-associated antigen C2 (MAGE-C2), also known as HCA587, is a member of the Type I Cancer-Testis Antigen (CTA) family, primarily expressed in the testis and various malignant tumors but absent in normal somatic tissues (UniProt: P43367). It plays a significant role in oncogenesis by forming a complex with TRIM28, which enhances the E3 ubiquitin ligase activity of TRIM28 toward the tumor suppressor p53, leading to its degradation and subsequent inhibition of apoptosis (PMID: 21148085). Because MAGE-C2 is an intracellular protein, it is targeted via its degradation products—short peptides presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, such as HLA-A*02:01 (PMID: 10449211). Therapeutic strategies focusing on this target include the development of engineered T-cell receptors (TCRs) for TCR-T cell therapy, which are designed to recognize these specific peptide-MHC complexes with high affinity. This approach allows for the precise elimination of MAGE-C2-positive cancer cells while sparing healthy tissues, making it a promising candidate for treating hepatocellular carcinoma, melanoma, and other MAGE-C2-expressing malignancies (NCT04729543). Additionally, MAGE-C2 has been explored as a target for cancer vaccines and monoclonal antibodies that recognize the peptide-MHC complex. The high specificity of its expression pattern minimizes the risk of on-target, off-tumor toxicity in non-germline tissues. Clinical monitoring of MAGE-C2 expression and HLA-type matching are essential for patient selection in these advanced immunotherapies.

Other names

HCA587Hepatocellular carcinoma-associated antigen 587Cancer/testis antigen 10CT10

T-cell receptor (TCR) recognition of MAGE-C2-derived peptides presented by MHC Class I molecules, triggering cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.