Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes

Background:Type 1 diabetes (T1D) is more than an insulin-deficiency disease-it is an autoimmune disease, and thefield ismoving toward adopting disease-modifying immunotherapy aspart of clinical care during T1D development.Summary:Recentsuccessful immunotherapies as well as therapies that missedthe mark are reviewed. T cell-directed therapies may allow forthe greatest preservation of beta cell function but also come withmore side effects. Anti-cytokine therapies are very promisingbut likely need chronic administration. Antigen-specificthera-pies while safe have not produced meaningful results. Mostsuccessful trials have been conducted in adolescents and adultswith stage 3 T1D (clinical T1D) with preserved C-peptide (up to60% more compared to placebo) demonstrated 1-2yearsposttreatment. HbA1c and total insulin dose are less likely to besignificantly different between treated and placebo groupsbecause most participants in studies are meeting glycemictargets and because of the heterogeneous nature of thesemeasures. In the prevention space (delaying progression fromstage 2 to stage 3 T1D), the outcome is more discrete, and a Tcell-directed therapy, teplizumab, has received FDA approval.Even negative studies with promising mechanistic and safetyprofiles have added value.KeyMessages:What is clear, a singleadministration or short courseof an immunotherapy is unlikelyto provide sustained freedom from exogenous insulin.(c) 2024 S. Karger AG, Basel