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Melanoma-associated antigen C2 (MAGE-C2) is a member of the cancer-testis antigen (CTA) family, which is characterized by restricted expression in the male germline and aberrant overexpression in various malignancies [1, 10]. When presented as a peptide (e.g., ALKDVEERV or LLFGLALIEV) by the Human Leukocyte Antigen A*02:01 (HLA-A*02:01) molecule on the surface of tumor cells, it forms a highly specific target for the immune system [1, 3]. This peptide-MHC complex is recognized by specific T-cell receptors (TCRs), making it a prime candidate for adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T) [2, 5]. Biologically, the MAGE-C2 protein functions as a regulator of E3 ubiquitin ligases like TRIM28 and MDM2, thereby influencing the stability of the tumor suppressor p53 and promoting tumor cell survival and proliferation [7, 12]. Therapeutic strategies targeting the MAGE-C2/HLA-A*02:01 complex aim to exploit its tumor-specific presentation to induce selective destruction of cancer cells while sparing normal somatic tissues [3, 5]. Clinical development is currently focused on TCR-T therapies for patients with MAGE-C2-positive tumors who also express the HLA-A*02:01 allele [5].
T-cell receptor (TCR) mediated cytotoxicity
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