Engineering immunotherapies for autoimmunity and cancer

Abstract:
Effective delivery of drugs to direct immune responses requires an understanding of biological barriers, physicochemical properties of drug molecules, formulation and transport in vivo. Designing molecular structures that persist at the administration site or that promote drainage to regional lymphatic networks may enhance immune responses while sparing immune-related adverse events. Here, drug transport and local elimination mechanisms will be overviewed. Then, examples of molecular designs to direct drug delivery will be presented. Autoimmune therapies were designed by our lab to promote the drainage of autoantigens to secondary lymphoid organs to treat autoimmune diseases. Specifically, the size and solubility of these molecular constructs were tuned to promote access to the lymphatic compartment and induce immune tolerance in mouse models of type 1 diabetes. Our lab has also recently explored the design of immunostimulants that persist in tumor tissue after intratumoral/perilesional injection. Intratumoral immunotherapy is proposed to work synergistically with checkpoint inhibitors making a nonresponsive ‘cold’ tumor ‘hot’ by recruiting and activating tumor infiltrating lymphocytes. This approach can suffer from systemic immune-related adverse reactions, however, if enough immunostimulant escapes the site of administration. Data on the use of electrostatic mechanisms to promote tumor retention will be presented. These examples underscore the need for rational design of drug molecules or formulations based upon the route of delivery and biological barriers encountered.

Bio:
Cory Berkland is the Mark and Becky Levin Professor in the Departments of Biomedical Engineering and Chemistry at Washington University in Saint Louis. Previously, he was the Solon E. Summerfield Professor in the Department of Pharmaceutical Chemistry and in the Department of Chemical Engineering at The University of Kansas. He received MS and PhD degrees from the Department of Chemical and Biomolecular Engineering at the University of Illinois in Urbana-Champaign and a BS degree in Chemical Engineering from Iowa State University in Ames. His lab studies pharmaceuticals and materials with an emphasis on molecular design and transport in the human body. He is a co-founder of Orbis Biosciences (acquired by Adare Pharmaceuticals), Savara Pharmaceuticals (NASDAQ:SVRA), Bond Biosciences, Kinimmune, Axioforce, and other start-ups. He has served as a board member, executive, and fundraiser for these companies.