Blockade of the Activation of T Cells Around β-Cell by the Targeted CTLA-4 Ig at the Surface of β-Cell

被引:0
作者
Qu, Wei [1 ]
Li, Lin [1 ]
Han, Chendong [1 ]
Li, Meihua [1 ]
Wang, Jing [1 ]
Yin, Chaohui [1 ]
Zhang, Jing [2 ]
Jiang, Zhaoshun [1 ]
机构
[1] Jinan Mil Gen Hosp, Dept Endocrinol, Jinan 250031, Peoples R China
[2] Jinan Mil Gen Hosp, Dept Cadre Ward 3, Jinan 250031, Peoples R China
基金
中国博士后科学基金;
关键词
Diabetes; beta-Cell; CTLA-4-Ig; Targeting; ScFv; CONTROLLED-TRIAL; DOUBLE-BLIND; C-PEPTIDE; TYPE-1; IMMUNOTHERAPY; RESPONSES; MELANOMA;
D O I
10.1007/s12013-014-0282-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Diabetes mellitus affects 347 million people worldwide, and over 80 % of diabetes deaths occur in low- and middle-income countries. Type 1 diabetes (T1D) is characterized by the attacks of the body's own immune system on the pancreatic beta-cells. In this work, we present a new CTLA-4 Ig targeting at the surface of beta-cell and prepare it from Escherichia coli aiming at clearing activated T cells around beta-cells and avoiding all-round decline in systematic immunity. This fusion protein is composed of CTLA-4-Ig part and beta-cell-targeting part, with properties of the therapeutic effect of CTLA-4-Ig and selective binding to beta-cells. In preliminary biological activity assay, our results verified the feasibility of beta-cell-targeting strategy and its activity of CTLA-4-Ig part. The fusion protein recognizes and binds specifically to CD80(+) and CD86(+) cells as well as beta-cell, but not to control cells, displaying the potential to be used as a feasible and effective treatment of T1D with lessened side effect.
引用
收藏
页码:913 / 918
页数:6
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