Postdoctoral Fellowship for Tobias Neef: Biodegradable PLG Nanoparticles for Tolerance Induction in Type 1 Diabetes

Treatment of type 1 diabetes (T1D) can lead to lifelong insulin dependency or unwanted immunosuppressive side-effects. Thus, we are seeking to provide better treatment options by using nanoparticles to induce immune tolerance, thereby protecting insulin-secreting pancreatic beta cells from pathogenic, autoreactive T cells. Our previous studies have shown that biodegradable, antigen-associated poly(lactide-co-glycolide) (PLG) nanoparticles are an effective way to induce immune tolerance. Autoantigens can either be encapsulated within (PLG(Ag)) or affixed to the surface (PLG-Ag). Using the nanoparticles, we have been able to provide protection against EAE, the murine model of multiple sclerosis, as well as models of allergic airway inflammation and transplant rejection. Furthermore, we have shown the success of this approach in two different diabetic mouse models involving adoptive transfer of transgenic T cells. Ultimately, we will use it to encapsulate islet cell antigens and protect wild type non-obese diabetic (NOD) mice from spontaneous development of diabetes. Additionally, we will attempt to determine the basis behind tolerance. Finally, we will attempt to optimize fabrication of the particles for translation to clinical use and begin to test particles in vitro for interaction with human cells.