Polymeric Nanocarriers Delay the Onset of Type 1 Diabetes in Nonobese Diabetic (NOD) Mice 2365

Abstract Description Introduction Teplizumab (Anti-CD3) is the first FDA-approved therapy to delay the onset of type 1 diabetes (T1D) and prolong insulin independence. However, this therapy comes with a high price tag and immunosuppressive adverse effects. We have previously demonstrated that rapamycin-loaded polymersome nanoparticles (rPS) induce immune antigen-specific tolerance towards transplanted fully-MHC mismatched islets via a costimulation blockade. To assess if this strategy can protect native islets and tolerize autoantigens, rPS was benchmarked against Anti-CD3 in a spontaneous T1D mouse model. Materials and Methods rPS was fabricated with the block copolymer poly(ethylene) glycol and polypropylene sulfide as previously described. At either 8 or 12 weeks old, female NOD mice received subcutaneous rPS injections or intravenous Anti-CD3 infusions. Results rPS protected beta cell activity and delayed the onset of T1D by 9 and 6 weeks relative to the untreated and Anti-CD3 groups, respectively. Anti-CD3-treated mice developed lymphopenia (100%) and leukopenia (37.5%) during treatment. Overall, rPS therapy showed superiority in T1D onset delay and side effect profile relative to Anti-CD3 treatment. Conclusion rPS is a promising early-intervention therapy to delay the onset of T1D. Our prior work demonstrates that rPS leverages antigen presenting cells to reprogram T cells for antigen-specific islet tolerance and can mitigate adverse events of chronic, nonspecific immunosuppression. Topic Categories Therapeutic Approaches to Autoimmunity (THER)