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Cancer immunotherapy using dendritic cells and chimeric monoclonal antibody which induce apoptosis

使用树突状细胞和诱导细胞凋亡的嵌合单克隆抗体进行癌症免疫治疗

基本信息

批准号：
12670431
负责人：
ISHIDA Sadao
金额：
$ 2.18万
依托单位：
Sapporo Medical University School of Medicin
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670431/
关键词：
dendritic cells LPS PSMA3 NAIP IAP immune complex gene analysis アポトーシスキメラ抗体 JNK ERK モノクローナル抗体 erbB-2

项目摘要

Dendritic cells (DCs), are the most important antigen presenting cells. Many recent studies have compared the function of immature and mature DCs, but there have been few reports of the molecular changes that occur in DCs during maturation. Here we report differential gene expression in immature DCs generated from peripheral blood monocytes compared with mature DCs. Gene expression was evaluated using the differential display method after activation of immature DCs with a low concentration of lipopolysaccaride to induce maturation. Proteasome subunit (PSMA3), TFEC isoform, and BTK region clone 2f10-rpi were transiently up-regulated. Tryptophanyl-tRNA synthetase and CD63 antigen were up-regulated for at least 24 hours. Neuronal apoptosis inhibitory protein (NAIP) and transforming growth factor beta-induced 68 kD protein were down-regulated. This is the first report of NAIP expression in human DCs, Comparing the expression of NAIP with that of other members of the inhibitor of apoptosis protein (IAP) family and the bcl-2 family, only NAIP was strongly expressed in immature DCs before stimulation by LPS. PSMA3 was also induced in DCs stimulated with immune complex. These findings might contribute to our understanding of DC maturation and the effectiveness of DC-based vaccines.

树突状细胞（Dendritic cells，DC）是最重要的抗原提呈细胞。近年来，许多研究比较了未成熟和成熟DC的功能，但关于DC成熟过程中发生的分子变化的报道很少。在这里，我们报告的差异基因表达的不成熟的树突状细胞产生的外周血单核细胞与成熟的树突状细胞相比。在用低浓度脂多糖激活未成熟DC以诱导成熟后，使用差异显示方法评估基因表达。蛋白酶体亚基（PSMA 3）、TFEC亚型和BTK区克隆2f 10-rpi瞬时上调。色氨酸-tRNA合成酶和CD 63抗原上调至少24小时。神经元凋亡抑制蛋白（NAIP）和转化生长因子β诱导的68 kD蛋白表达下调。这是首次报道NAIP在人DC中的表达。与凋亡抑制蛋白（IAP）家族和bcl-2家族的其他成员相比，在LPS刺激前，NAIP在未成熟DC中仅强表达。在用免疫复合物刺激的DC中也诱导了PSMA 3。这些发现可能有助于我们理解DC成熟和基于DC的疫苗的有效性。