title: A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of type 1 diabetes in NOD mice.
abstract: To prepare a novel Bispecific Antibody (BsAb) as a potential targeted therapy for T1D, we produced a "functionally inert" monoclonal antibody (mAb) against Glucose transporter-2 (GLUT-2) expressed on β-cells to serve as an anchoring antibody. The therapeutic arm is an agonistic mAb against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), a negative regulator of T-cell activation expressed on activated CD4+ T-cells. A BsAb was prepared by chemically coupling an anti-GLUT2 mAb to an agonistic anti-CTLA-4 mAb. This BsAb was able to bind to GLUT2 and CTLA-4 in vitro, and to pancreatic islets, both in vitro and in vivo. We tested the safety and efficacy of this BsAb by treating Non-Obese Diabetes (NOD) mice and found that it could delay the onset of diabetes with no apparent undesirable side effects. Thus, engagement of CTLA-4 on activated T cells from target tissue can be an effective way to treat type-1 diabetes.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA.
authors.forename: Palash
authors.initials: P
authors.lastname: Bhattacharya
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA.
authors.forename: Jilao
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Haddad
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA.
authors.forename: Abdul
authors.initials: A
authors.lastname: Essani
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Gopisetty
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Elshabrawy
authors.affiliation: Department of Surgery, Hollings Cancer Centre, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Chenthamarakshan
authors.initials: C
authors.lastname: Vasu
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 606012, USA. Electronic address: bprabhak@uic.edu.
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D051273:Glucose Transporter Type 2 / Q000096:biosynthesis / Q000276:immunology; D050417:Insulin-Secreting Cells / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D016207:Cytokines; D051273:Glucose Transporter Type 2; D011994:Recombinant Proteins
keywords: Anti-CTLA-4; Anti-Glut2; Dendritic cells; Diabetes; Regulatory T cells; Tolerance