PHARAOH: A PHase I Trial Of Autologous Regulatory T Cell Therapy for AutOimmune Hepatitis

The goal of this project is to test a new cell therapy (regulatory T cells or Tregs) developed by investigators at Northwestern for a disease called autoimmune hepatitis (AIH). This disease is characterized by inflammation of the liver that can lead to severe liver damage and even the need for liver transplantation. The current treatment involves the use of long term immunosuppressive drugs that keep the disease in remission but need to be given for life in most patients. As these drugs supress the immune system, they can cause side effects and increase the risk of serious complications, such as cancer and infection. A major advance would be to find a treatment that could control the disease but not suppress the immune system. At Northwestern, we have been able remove certain cells called Tregs, expand them in our laboratory, and give them back safely to kidney transplant recipients. Tregs can potentially control inflammation and might be a safer alternative to immunosuppression. In addition, one of the reasons why patients develop AIH is that they have a low amount of Tregs, so expanding them and giving them back might restore a balance in the immune system to allow for removal of the drugs. This project will test this approach in 15 AIH patients, by giving the patients their own expanded Tregs and removing the immunosuppressive drugs. A main goal is to ensure that giving the Tregs are safe, and we expect that this will be safe like our experience in kidney transplant recipients. The other main goal is to see where the Tregs go and how long they stay in the body after they are given. With specific tests, we can determine if these Tregs stay in the blood and/or go into the liver itself to control the inflammation and not let patients have disease relapse. These goals will provide the initial information we need to design larger studies where we can better compare standard approaches versus using Tregs to increase the ability to remove immunosuppressive drugs. This unique approach could lead to improved health outcomes by lowering the side effects, risks and costs of these medications in this population.