首页> 外文期刊>International immunopharmacology >New polycomb group protein enhancer of zeste homolog (EZH) 2-derived peptide with the potential to induce cancer-reactive cytotoxic T lymphocytes in prostate cancer patients with HIA-A3 supertype alleles
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New polycomb group protein enhancer of zeste homolog (EZH) 2-derived peptide with the potential to induce cancer-reactive cytotoxic T lymphocytes in prostate cancer patients with HIA-A3 supertype alleles

机译:Zeste同源物(EZH)2-衍生的肽的新多元群组蛋白增强剂,其潜力诱导癌症癌症患者的癌症反应性细胞毒性T淋巴细胞HIA-A3超型等位基因

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Analyses on reactivity of anti-cancer cytotoxic T lymphocytes (CTLs) and clinical application of peptide-based anti-cancer vaccine have been mainly focused on patients with HLA-A2 or -A24 alleles. In this study, we identified an enhancer of zeste homolog (EZH) 2-derived peptide applicable for anti-cancer vaccine for prostate cancer patients with HLA-A3 supertype alleles. Five EZH2-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were functionally screened for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A3 supertype allele prostate cancer patients. As a result, EZH2(733-741) peptide was found to efficiently induce peptide-specific CTLs. The EZH2(733-741) peptide-stimulated and purified CD8(+) T cells from PBMCs of HLA-A3 supertype allele + prostate cancer patients showed higher cytotoxicity against HLA-A3 supertype allele-expressing LNCaP prostate cancer cells than against parental LNCaP cells. This cytotoxicity against HLA-A3 supertype allele-expressing LNCaP cells was partially but significantly inhibited by the addition of EZH2(733-741) peptide-pulsed competitive cells. These results indicate that the EZH2(733-741) peptide could be a promising candidate for peptide-based immunotherapy for HLAA3 supertype allele(+) prostate cancer patients. (C) 2015 Elsevier B.V. All rights reserved.
机译:抗癌细胞毒性T淋巴细胞(CTL)反应性分析以及肽基抗癌疫苗的临床应用主要集中在HLA-A2或-A24等位基因患者上。在这项研究中,我们确定了适用于抗癌疫苗的Zeste同源物(EZH)2-衍生肽的增强剂,用于患有HLA-A3超型等位基因的前列腺癌患者。在基于结合基序法制备的五种EzH2衍生的肽,其在功能上筛选用于HLA-A3超卵型等位基因(HLA-A11,-A31和-A33)的潜力,以诱导来自外周血单核细胞的肽特异性CTL( HLA-A3超卵型等位基因前列腺癌患者的PBMCs。结果,发现EZH2(733-741)肽有效地诱导肽特异性CTL。来自HLA-A3超卵型等位基因+前列腺癌患者的PBMC的肽刺激和纯化的CD8(+)T细胞显示出对HLA-A3超卵巢等位基因的表达LNCAP前列腺癌细胞的细胞毒性高于父母的LNCAP细胞。通过添加EZH2(733-741)肽 - 脉冲竞争性细胞,这种对HLA-A3超卵型等位基因表达的LNCAP细胞的细胞毒性部分但显着抑制。这些结果表明,EZH2(733-741)肽对于HLAA3超卵巢等位基因(+)前列腺癌患者的基于肽的免疫疗法可能是一个很有希望的候选者。 (c)2015 Elsevier B.v.保留所有权利。

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