Designing synthetic suppressor cell therapeutics for Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) is a chronic disease that affects the intestines and causes uncontrolled inflammation. To treat it, we currently use medicines that broadly block the immune system to calm down the inflammation. But these medicines have side effects – your immune system normally helps protect from infections and cancer, and the risk for those complications can increase if your immune system is broadly suppressed. We propose to develop a targeted anti-inflammatory treatment that would only act where it is needed – for IBD, in the gut. We are able to engineer immune cells to give them new capabilities. Our plan is to take T cells, which normally cause inflammation, and redesign them to have them suppress the immune system when and where we want. To do so, we will use synthetic receptors that our research group developed called “synthetic Notch” or synNotch. These reprogrammed T cells, which we call synthetic suppressor cells, will be able to sense when they are in the gut and then respond by producing anti-inflammatory signals. This should achieve local suppression of the immune system only in the diseased organ. We will also design suppressors to target a specific type of inflammation that contributes to IBD.