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白细胞介素-12 质粒 DNA 修饰的树突状细胞增强抗肿瘤作用。

Augmented anti-tumor effect of dendritic cells genetically engineered by interleukin-12 plasmid DNA.

机构信息

Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

出版信息

J Biomater Sci Polym Ed. 2010;21(5):659-75. doi: 10.1163/156856209X434674.

Abstract

The objective of this study was to genetically engineer dendritic cells (DC) for biological activation and evaluate their anti-tumor activity in a tumor-bearing mouse model. Mouse DC were incubated on the surface of culture dishes which had been coated with the complexes of a cationized dextran and luciferase plasmid DNA complexes plus a cell adhesion protein, Pronectin, for gene transfection (reverse transfection). When compared with the conventional transfection where DC were transfected in the medium containing the complexes, the level of gene expression by the reverse method was significantly higher and the time period of gene expression was prolonged. Following the reverse transfection of DC by a plasmid DNA of mouse interleukin-12 (mIL-12) complexed with the cationized dextran, the mIL-12 protein was secreted at higher amounts for a longer time period. When injected intratumorally into mice carrying a mass of B16 tumor cells, the DC genetically activated showed significant anti-tumor activity.

摘要

本研究的目的是通过基因工程对树突状细胞(DC)进行生物激活,并在荷瘤小鼠模型中评估其抗肿瘤活性。将小鼠 DC 孵育在已涂覆阳离子化葡聚糖和荧光素酶质粒 DNA 复合物加细胞黏附蛋白 Pronectin 的培养皿表面上,进行基因转染(反向转染)。与传统的将 DC 转染到含有复合物的培养基中的转染方法相比,反向方法的基因表达水平显著更高,且基因表达的时间延长。用与阳离子化葡聚糖结合的小鼠白细胞介素-12(mIL-12)质粒 DNA 对 DC 进行反向转染后,mIL-12 蛋白的分泌量更高,时间更长。当将经基因激活的 DC 瘤内注射到携带大量 B16 肿瘤细胞的小鼠中时,显示出显著的抗肿瘤活性。

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