title: 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.
authors.affiliation: Endocrinology Department, Jinan Military General Hospital, Jinan, 250031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Chendong
authors.initials: C
authors.lastname: Han
authors.forename: Meihua
authors.initials: M
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Chaohui
authors.initials: C
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhaoshun
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018796:Immunoconjugates / Q000235:genetics / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D000069594:Abatacept