Identification of an HLA-A*0201-restrictive CTL epitope from MUC4 for applicable vaccine therapy

Identification of an HLA-A*0201-restrictive CTL epitope from MUC4 for applicable vaccine therapy
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从 MUC4 中鉴定 HLA-A*0201 限制性 CTL 表位,用于适用的疫苗治疗

DOI:
10.1080/08923970902795203
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发表时间:
2009
影响因子:
3.3
通讯作者:
Y. Miao
Y. Miao
中科院分区:
医学4区
文献类型:
--
作者:
Junli Wu;Jishu Wei;Kai Meng;Jian;Wen;Jing;Zekuan Xu;Y. Miao

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最近的研究表明,MUC 4在许多肿瘤的发展中起着重要作用,并可能被证明是一种新的癌症免疫治疗靶点。我们的目的是确定癌症相关抗原MUC 4的HLA-A*0201限制性细胞毒性T淋巴细胞(CTL)表位。使用HLA结合预测软件扫描MUC 4序列的免疫原性肽。用细胞因子诱导外周血单个核细胞(PBMC)分化为树突状细胞(DC)。通过软件分析选择五个可能的CTL表位,合成并用于脉冲成熟DC。来自HLA-A*0201健康供体的PBMC的CD 8 + T细胞用自体MUC 4肽负载的DC刺激并体外扩增。通过ELISPOT评估T细胞活化,并通过51铬(51 Cr)释放试验测定细胞毒性。结果表明,P01204肽诱导的CTL能裂解P01204肽致敏的T2细胞和HCT-116细胞(MUC 4+,HLA-A2+)。与对照肽相比,P01204增加了产生IFN-γ的T细胞的数量。总之,这些结果表明,P01204是一种新的HLA-A*0201限制性CTL表位的癌症相关抗原MUC 4。这将为肿瘤特异性肽疫苗的研制奠定基础。
Recent research has indicated that MUC4 plays an important role in the development of many tumors and may prove useful as a novel cancer immunotherapy target. We aimed to identify HLA-A*0201-restrictive cytotoxic T lymphocyte (CTL) epitopes of the cancer-associated antigen MUC4. The MUC4 sequence was scanned for immunogenic peptides using HLA-binding prediction software. Dendritic cells (DCs) from peripheral blood mononuclear cells (PBMCs) were induced by cytokines. Five possible CTL epitopes were selected by software analysis, synthesized, and used to pulse mature DCs. The CD8+ T cells from PBMCs from an HLA-A*0201 healthy donor were stimulated with autologous MUC4-peptide-loaded DCs and expanded in vitro. T cell activation was assessed by ELISPOT, and cytotoxicity was determined by 51chromium (51Cr)-release assays. Our results show that CTLs induced by peptide P01204 could lyse T2 cells pulsed with peptide P01204 and HCT-116 cells (MUC4+, HLA-A2+). Compared with a control peptide, P01204 increased the number of IFN-γ producing T cells. Overall, these results suggest that P01204 is a novel HLA-A*0201-restrictive CTL epitope of the cancer-associated antigen MUC4. This will provide a foundation for the development of tumor-specific peptide vaccines.
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发表时间: 2002-08-01
期刊: EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子: --
作者:
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发表时间: 2006-06-01
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