SBIR Phase I: An Engineering Platform for Adaptive Medicines

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a cell-based platform technology that can sense inflammatory sites and respond by producing anti-inflammatory factors to treat autoimmune diseases. There are more than 80 types of autoimmune disease with more than 23.5 million Americans affected. Autoimmune diseases are the number one cause of morbidity for women in the U.S., and one of the top 10 causes of death for women under 65 years old. The annual healthcare burden of these diseases is estimated at more than $100 billion in the U.S. alone. Current treatments for autoimmune diseases are effective for some patients, but a majority either do not respond or become refractory. Furthermore, standard drugs result in systemic immune suppression, which can cause severe and chronic side effects. Hence, there is substantial market need for anti-inflammatory drugs that can act locally at the site of inflammation, and deliver the "right dose at the right time" depending on the severity of the flare. If successful, the adaptive cell therapy platform being developed in this proposal will serve as the basis for a next-generation therapy to existing biologics. This SBIR Phase I project proposes to develop a cell-based technology that localizes to a site of inflammation, senses inflammatory signals, and triggers the release of anti-inflammatory agents. The substantial technical and clinical progress made in recent years in synthetic biology and cell therapies is enabling development of this type of product. The goal is to design and optimize synthetic gene circuits to program cells to locally sense inflammatory signals such as TNFalpha and release anti-TNF drugs. The plan is to introduce these circuits into adult stem cells that have been used safely in numerous clinical trials against autoimmune diseases and have a well-established commercial development path. The engineered cells will be tested in culture to show input/output response to different levels of TNFalpha, and then tested in mouse models of disease. If successful, lead candidates will be further developed in a Phase II application.