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
Jiandong Z et al. – This study discussed the prediction, synthesis, and testing of a series of human leukocyte antigen (HLA)–A2Ârestricted 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–A11Âexpressing breast cancer cells but not MAGE–A11Ânegative 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–A11Âspecific CTL.
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