title: Non-antigenic and antigenic interventions in type 1 diabetes.
abstract: Type 1 diabetes (T1D) results from autoimmune destruction of the pancreatic β-cells. Current T1D therapies are exclusively focused on regulating glycemia rather than the underlying immune response. A handful of trials have sought to alter the clinical course of T1D using various broad immune-suppressors, e.g., cyclosporine A and azathioprine.(1-3) The effect on β-cell preservation was significant, however, these therapies were associated with unacceptable side-effects. In contrast, more recent immunomodulators, such as anti-CD3 and antigenic therapies such as DiaPep277, provide a more targeted immunomodulation and have been generally well-tolerated and safe; however, as a monotherapy there appear to be limitations in terms of therapeutic benefit. Therefore, we argue that this new generation of immune-modifying agents will likely work best as part of a combination therapy. This review will summarize current immune-modulating therapies under investigation and discuss how to move the field of immunotherapy in T1D forward.
authors.affiliation: Type 1 Diabetes R&D Center; Novo Nordisk Inc.; Seattle, WA USA; Pacific Northwest Diabetes Research Institute; Seattle, WA USA.
authors.forename: Anna K E
authors.initials: AK
authors.lastname: Rydén
authors.forename: Johnna D
authors.initials: JD
authors.lastname: Wesley
authors.forename: Ken T
authors.initials: KT
authors.lastname: Coppieters
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Von Herrath
mesh_terms: D017252:CD3 Complex / Q000276:immunology; D018834:Chaperonin 60 / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D017252:CD3 Complex; D018834:Chaperonin 60; C447781:DiaPep 277; D007155:Immunologic Factors; D007328:Insulin; D010446:Peptide Fragments
keywords: Anti-CD3; Antigenic immune-modulation; DiaPep277; GAD65; Immunomodulation; Insulin; Type 1 Diabetes