Hepatitis B virus (HBV) is the most common cause of liver cancer in the world, resulting in approximately 880,000 deaths from liver cirrhosis and hepatocellular carcinoma/liver cancer (HCC) combined. Now new research from UCL shows it is possible to use immunotherapy to treat chronic HBV. The study was published recently in Nature Communications.
Lead author Professor Mala Maini of the UCL Division of Infection & Immunity commented: "Chronic hepatitis B virus infection is a major global health problem and the most common cause of liver cancer in the world. The development of novel therapeutic options is crucial to improve patient care. Immune cells such as T cells are indispensable for fighting viruses and tumors but are often highly dysfunctional and fail to control these diseases. The current standard of care treatments are often incapable of eliminating the virus, do not prevent cancer development, and do not rescue immune cells. In this study, we aimed to identify a treatment target to directly inhibit the virus while also boosting the immune cells fighting it."
The newly developed immunotherapy targets an enzyme called acyl-CoA:cholesterol acyltransferase (referred to as ACAT) to elicit an immune response. ACAT plays a role in managing levels of cholesterol in cells and by inhibiting it, it is possible to amp up specific immune cells to attack both cancer cells and the virus itself.
First author Dr. Nathalie Schmidt explained: "We have found a highly effective novel target for the treatment of chronic hepatitis B virus infection and liver cancer. Modulating cholesterol metabolism with ACAT inhibitors has the unique features of directly targeting the virus and tumors while at the same time boosting the T cells that fight them. This enables us to tackle the disease from multiple directions at the same time."
The best part, adds Dr. Schmidt, is that it’s possible to use an already-approved drug that has both antiviral and immunotherapeutic effects. "The cholesterol-modifying drug is already known to be safe in humans and we hope that our study now informs the development of clinical trials combining cholesterol modulation with other immunotherapies. In summary, our findings offer exciting new possibilities for the treatment of patients with chronic viral infections and cancer."