The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy†,Biomaterials Science

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The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy†
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-01-24 00:00:00 , DOI: 10.1039/c7bm01143a
Pingzhang Chen _{1,

2,

3,

4,

5} , Yunhong Liu _{6,

7,

8,

9} , Jing Zhao _{1,

2,

3} , Xiaojuan Pang _{1,

2,

3} , Peifa Zhang _{1,

2,

3} , Xiaohu Hou _{1,

2,

3} , Ping Chen _{1,

2,

3} , Cheng-yi He _{1,

2,

3} , Zhiyong Wang _{1,

1,

2,

3,

10} , Zhi-ying Chen _{1,

2,

3,

4,

5}

Affiliation

Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD₃ ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic–inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro. Furthermore, the gene production, anti-IGF1R/CD3 bispecific T-cell engager, exhibited a rapid redirection activity in T cells to induce cancer cell apoptosis. In summary, the results confirmed that stPEI-CaP could be an efficient gene delivery system for BiTE encoding MC.DNA based gene immunotherapy.

中文翻译：

两亲聚乙烯亚胺/磷酸钙复合物的合成，用于基于双特异性T细胞接合剂的免疫基因治疗†

双特异性T细胞衔接子（BiTE）是具有特定结构的单链可变片段，可以连接癌细胞上的表面抗原和T细胞上的CD ₃配体，然后接合T细胞进行癌症免疫疗法。在本报告中，使用了一种由硬脂酸修饰的聚乙烯亚胺（stPEI）和磷酸钙（CaP）组成的新型有机-无机杂种基因传递系统，将MC.DNA传递到细胞中以表达BiTE抗体。该基因传递系统在体外显示出高转染效率，长期作用和低细胞毒性。此外，抗IGF1R / CD3双特异性T细胞接合子的基因产生在T细胞中表现出快速的重定向活性，从而诱导癌细胞凋亡。总之，结果证实stPEI-CaP可能是BiTE编码基于MC.DNA的基因免疫疗法的有效基因传递系统。

更新日期：2018-01-24

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