Background & Purpose

JDRF is soliciting letters of intent (LOI) for the discovery, development and pre-clinical testing of tolerogenic delivery systems (TDS) of diabetes-specific autoantigens designed to prevent and/or reverse type 1 diabetes (T1D). JDRF is committed to translation of research findings towards clinical results and is most interested in projects that have clinical translation potential.

Inducing antigen-specific tolerance is one of the most elusive and most highly sought therapeutic goals in autoimmune diseases. Unfortunately, several independent disease prevention and treatment trials with antigen specific immunotherapies (ASIs) have been generally disappointing with respect to metabolic disease outcomes and no treatment has been shown to induce durable immune tolerance. These studies, nevertheless, provide compelling evidence of transiently enhanced regulatory T (Treg) cell number and function, and reduced effector T cell (Teff) cell numbers suggesting that immune tolerance might be achieved with the appropriate improvements to ASI therapy. Because most of these ASIs were comprised of antigen only, improvements can be made to enhance the potency of ASIs with toleranceinducing agents. Tolerance delivery systems, e.g., tolerance-inducing adjuvants, can be combined with autoantigen to achieve such an improvement in ASI potency. Several tolerance-inducing ASIs have been described and tested in preclinical models which showed an ability of ASIs to enhance various types of Treg cells that could suppress specific pathogenic autoimmune responses. It should be noted that such approaches offer a platform technology that can be applied to other autoimmune and allergic conditions with the provision of disease-relevant antigen(s).