Immune-checkpoint engineered colon organoids to induce immune tolerance as treatment for Inflammatory Bowel Disease (IBD).

Despite intense research efforts on Inflammatory Bowel Diseases (IBD), there are no treatments that result in a sustained return to normal. Thus, there is an urgent need to develop innovative treatment approaches. Applying lessons learned from cancer immunotherapy, we have developed a novel treatment aimed at curing IBD: injectable Colon Organoid Immune Niche (COIN). Using chemical reactions, we engineered colon cells with high levels of immune suppressive molecules to formulate COIN. We showed that these engineered cells were able to suppress immune reaction to the colon and induce tolerance in several mouse models of colitis. Based on this exciting preliminary data, we aim to further improve COIN technology to enable clinical translation into human trials. To accomplish this, we will engineer COINs with different combinations of immune suppressive molecules and identify the most effective ones in mouse models of IBD.ÊIn addition, we aim to better understand the mechanisms of action of COIN therapy in IBD by characterizing the changes in the immune system. Success of our proposed work can result in a new and curative treatment for IBD. Given the high cost and high morbidity associated with IBD, COIN can be a disruptive technology/treatment for IBD and other autoimmune diseases.