Overcoming challenges in treating autoimmuntity: Development of tolerogenic immune-modifying nanoparticles

Autoimmune diseases, such as celiac disease, multiple sclerosis, and type 1 diabetes, are leading causes of morbidity and mortality in the United States. In these disease states, immune regulatory mechanisms fail that result in T and B cell-mediated destruction of self-tissues. The known role of T cells in mediating autoimmune diseases has led to the emergence of numerous therapies aimed at inactivating T cells, however successful 'tolerance-inducing' strategies have not yet emerged for approved standard-of-care clinical use. In this review, we describe relevant examples of antigen-specific tolerance approaches that have been applied in clinical trials for human diseases. Furthermore, we describe the evolution of biomaterial approaches from cell-based therapies to induce immune tolerance with a focus on the Tolerogenic Immune-Modifying nanoParticle (TIMP) platform. The TIMP platform can be designed to treat various autoimmune conditions and is currently in clinical trials testing its ability to reverse celiac disease. (C) 2018 Elsevier Inc. All rights reserved.