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Zebularine treatment induces MAGE-A11 expression and improves CTL cytotoxicity using a novel identified HLA-A2-restricted MAGE-A11 peptide

Journal of Immunotherapy Aug 24, 2017

Melanoma–associated antigen–A11 (MAGE–A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE–A11 is a potential immunotherapy target in breast cancer. MAGE–A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of

Jiandong Z et al. – This study discussed the prediction, synthesis, and testing of a series of human leukocyte antigen (HLA)–A2–restricted candidate melanoma–associated antigen A11 (MAGE–A11) peptides. Of all the peptides, p–350 elicited peptide–specific cytotoxic T–lymphocytes (CTLs) from healthy HLA–A*0201–positive donors, which can lyse MAGE–A11–expressing breast cancer cells but not MAGE–A11–negative tumor cells. The anti–tumor response was improved by using zebularine, which is a deoxyribose nucleic acid methyltransferase inhibitor. The results demonstrated that peptide p350 is a potential candidate for tumor vaccination or T–cell therapy as it induced peptide–specific cytotoxic activity. In addition, zebularine–mediated epigenetic modulation was shown to induce MAGE–A11 expression in breast cancer cells and enable cytotoxicity by MAGE–A11–specific CTL.

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