The Synthesis of Amphiphilic Polyethyleneimine/Calcium Phosphate Composites for Bispecific T-cell engager based Immunogene therapy

Pingzhang Chen, Yunhong Liu, Jing Zhao, Xiaojuan Pang, Peifa Zhang, Xiaohu Hou, Ping Chen, Cheng-Yi He, Zhiyong Wang, Zhi-Ying Chen

Index: 10.1039/C7BM01143A

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Abstract

Bispecific T-cell engagers (BiTEs) are single chain variable fragment with specific structure, which could connect the surface antigen on cancer cells and CD3 ligand on T cells, and then engage T cells for cancer immunotherapy. In this report, a novel organic-inorganic hybrid gene delivery system composed by stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to delivery 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 the BiTE encoding MC.DNA based gene immunotherapy.