Robert N Bone1,2, Carmella Evans-Molina3,4,5,6,7,8. 1. Department of Medicine, Indiana School of Medicine, 635 Barnhill Dr, MS 2031A, Indianapolis, IN, 46202, USA. 2. Center for Diabetes & Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. 3. Department of Medicine, Indiana School of Medicine, 635 Barnhill Dr, MS 2031A, Indianapolis, IN, 46202, USA. cevansmo@iu.edu. 4. Center for Diabetes & Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu. 5. Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu. 6. Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu. 7. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu. 8. Roudebush VA Medical Center, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.
Abstract
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D. RECENT FINDINGS: Combination immunotherapies have had mixed results in improving short-term glycemic control and insulin secretion in recent-onset T1D. A handful of studies have successfully reached their primary end-point of improved insulin secretion in recent-onset T1D. However, long-term improvements glycemic control and the restoration of insulin independence remain elusive. Future interventions should focus on strategies that combine immunomodulation with efforts to alleviate β-cell stress and address the formation of antigens that activate autoimmunity.
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D. RECENT FINDINGS: Combination immunotherapies have had mixed results in improving short-term glycemic control and insulin secretion in recent-onset T1D. A handful of studies have successfully reached their primary end-point of improved insulin secretion in recent-onset T1D. However, long-term improvements glycemic control and the restoration of insulin independence remain elusive. Future interventions should focus on strategies that combine immunomodulation with efforts to alleviate β-cell stress and address the formation of antigens that activate autoimmunity.
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