1. InsB9-23 Gene Transfer to Hepatocyte-Based Combined Therapy Abrogates Recurrence of Type 1 Diabetes After Islet Transplantation
- Author
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Francesca Sanvito, Paolo Monti, Maria Grazia Roncarolo, Fabio Russo, Giorgia Squeri, Antonio Citro, Andrea Annoni, and Silvia Gregori
- Subjects
Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Autoimmunity ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,Mice ,Mice, Inbred NOD ,Recurrence ,Insulin-Secreting Cells ,Internal Medicine ,medicine ,Secondary Prevention ,Animals ,NOD mice ,Type 1 diabetes ,geography ,geography.geographical_feature_category ,business.industry ,Graft Survival ,Gene Transfer Techniques ,FOXP3 ,Immunotherapy ,medicine.disease ,Islet ,Transplantation ,Diabetes Mellitus, Type 1 ,Cancer research ,Hepatocytes ,business ,Peptides ,Insulitis - Abstract
The induction of antigen (Ag)-specific tolerance represents a therapeutic option for autoimmune diabetes. We demonstrated that administration of a lentiviral vector enabling expression of insulin B chain 9-23 (InsB9-23) (LV.InsB) in hepatocytes arrests β-cell destruction in prediabetic NOD mice by generating InsB9-23–specific FoxP3+ T regulatory cells (Tregs). LV.InsB in combination with a suboptimal dose of anti-CD3 monoclonal antibody (combined therapy [CT], 1 × 5 μg [CT5]) reverts diabetes and prevents recurrence of autoimmunity after islet transplantation in ∼50% of NOD mice. We investigated whether CT optimization could lead to abrogation of recurrence of autoimmunity. Therefore, alloislets were transplanted after optimized CT tolerogenic conditioning (1 × 25 μg [CT25]). Diabetic NOD mice conditioned with CT25 when glycemia was
- Published
- 2019