The Role of Gastrointestinal GLP-1R Neurons in Mediating the Glucose-Lowering and Weight Loss Effects of Oral Exendin-4

Type 1 diabetes is an autoimmune disease caused by the attack of T cells on the insulin-producing cells in the pancreas, making these T cells an ideal target for new treatments. Recently, teplizumab, a monoclonal antibody treatment, was approved by the FDA for the prevention of type 1 diabetes in high-risk patients. Chimeric Antigen Receptors (CARs) are a new technology which retargets a patient's own T cells against disease-causing cells and has resulted in breakthrough successes and FDA approval to treat diseases such as leukemia. CAR T cell technology offers multiple advantages over monoclonal antibody therapy including more thorough and more long-lasting killing of the immune cells responsible for the damage to the pancreas. Our long-term goal is to develop CAR therapies for type 1 diabetes in humans, so here we propose developing our previous CAR T cell designs into useful formats to test in a mouse model of type 1 diabetes. This is an important step in proving that this cutting-edge technology can be applied to type 1 diabetes, allowing us to improve our CAR T cell technology and understand how the immune system responds. This data is critical for the development of this technology into a treatment that can one day be used in patients.