Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes.

backgroundType 1 diabetes (T1D) is more than an insulin-deficiency disease - it is an autoimmune disease, and the field is moving toward adopting disease-modifying immunotherapy as part of clinical care during T1D development. SUMMARY: Recent successful immunotherapies as well as therapies that missed the mark are reviewed. T cell-directed therapies may allow for the greatest preservation of β cell function but also come with more side effects. Anti-cytokine therapies are very promising but likely need chronic administration. Antigen-specific therapies while safe have not produced meaningful results. Most successful trials have been conducted in adolescents and adults with stage 3 T1D (clinical T1D) with preserved C-peptide (up to 60% more compared to placebo) demonstrated 1-2 years post treatment. HbA1c and total insulin dose are less likely to be significantly different between treated and placebo groups because most participants in studies are meeting glycemic targets and because of the heterogeneous nature of these measures. In the prevention space (delaying progression from stage 2 to stage 3 T1D), the outcome is more discrete, and a T cell-directed therapy, teplizumab, has received FDA approval. Even negative studies with promising mechanistic and safety profiles have added value. KEY MESSAGES: What is clear, a single administration or short course of an immunotherapy is unlikely to provide sustained freedom from exogenous insulin.