Redirecting T cells to overcome tolerance in chronic HBV infection

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Hepatitis B virus remains one of the top ten killers in the world today, causing around a million deaths every year from chronic liver disease. There is a vaccine to prevent spread, but this is of no use to the 400 million people estimated to already be chronically infected. There are now a number of drugs available to treat hepatitis B infection but these typically only suppress the virus rather than clear it; when the patient stops the treatment the virus level comes back up. There is no effective drug therapy for the end-stage complications of liver failure and liver cancer.The goal of the work proposed here is to allow us to develop a type of treatment to safely boost immune control of hepatitis B virus infection. We would like to harness the natural ability of a component of the immune system called T cells to control this virus. There are very few of the right type of T cells left in patients with chronic hepatitis B virus infection, so we will genetically engineer the patients? T cells to regain the ability to fight against hepatitis B virus. This proposal aims to look into how effective these genetically engineered T cells will be at combatting hepatitis B virus when it is in the liver, by mimicking this situation in a test tube and in a mouse model. Our findings will provide essential information for the future application of this approach to hepatitis and other chronic infections and tumours.