Engineering extracellular vesicle-based vaccines against type 1 diabetes – 2EVAD

Type 1 diabetes (T1D) is an autoimmune disease caused by the progressive loss of tolerance towards antigens of insulin-producing pancreatic beta cells leading to their destruction and chronic hyperglycemia. The steeply rising disease incidence suggests an urgent need to develop new treatment strategies to restore antigen-specific tolerance. Extracellular vesicles (EV) released by living cells have entered the phase of clinical evaluation as diagnostic and therapeutic tools for drug delivery and immune intervention. Less complex than their cell of origin and non-replicative, EV present excellent biosafety andbiocompatibility profiles, supplanting synthetic vehicle formulations. In particular, EV from immune-regulatory cells such as mesenchymal stem cells have shown to conserve their parental cell’s outstanding immunoregulatory properties. The aim of this project is to develop a new patient-tailored vaccination strategy for T1D by engineering tolerogenic EV expressing candidate T1D antigens to induce long lasting adaptive immune tolerance. To this end, the consortium gathers the IECM pluridisciplinary research team with solid experience in the fields of T1D and EV research, the Ciloa Company with a unique patent to customize EV, and clinicians from Nantes university Hospital involved in clinical research on T1D immune intervention. The experimental proof for T1D in the project will be an important step towards the development of a new generation of tolerogenic EV-based vaccines to treat inflammatory and autoimmune diseases.