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The Melanoma-associated antigen 2 (MAGE-A2) peptide presented by HLA-A*02:01 is a peptide-major histocompatibility complex (pMHC) that serves as a specific target for cancer immunotherapy (ACROBiosystems). MAGE-A2 is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in the testis and placenta but is aberrantly re-expressed in various malignancies, including melanoma, lung, and breast cancers (NIH/PubMed). The specific decameric peptide YLQLVFGIEV (residues 157-166) is processed from the intracellular MAGE-A2 protein and presented on the cell surface by the HLA-A*02:01 allele (Cosmo Bio). This complex is recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, triggering an immune response against the tumor cells (NIH/PubMed). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, peptide-based vaccines such as IDM-2101, and TCR-mimetic antibodies (ASCO/JCO, NIH/J. Immunol.). Because MAGE-A2 is not expressed in normal adult tissues, it offers a wide therapeutic window, although potential cross-reactivity with other MAGE family members remains a safety consideration (Frontiers in Oncology). Additionally, epigenetic modulators like 5-azacytidine are used to upregulate MAGE-A2 expression, enhancing the visibility of tumor cells to the immune system (NIH/PubMed). Clinical trials have explored these modalities in patients with advanced solid tumors who possess the HLA-A*02:01 genotype (ASCO/JCO, MDPI).
Targeted T-cell mediated cytotoxicity and epigenetic upregulation of antigen expression.
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