Blockade of the activation of T cells around β-cell by the targeted CTLA-4 Ig at the surface of β-cell.

Abstract

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 β-cells. In this work, we present a new CTLA-4 Ig targeting at the surface of β-cell and prepare it from Escherichia coli aiming at clearing activated T cells around β-cells and avoiding all-round decline in systematic immunity. This fusion protein is composed of CTLA-4-Ig part and β-cell-targeting part, with properties of the therapeutic effect of CTLA-4-Ig and selective binding to β-cells. In preliminary biological activity assay, our results verified the feasibility of β-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 β-cell, but not to control cells, displaying the potential to be used as a feasible and effective treatment of T1D with lessened side effect.