The hepatitis B virus (pictured) causes chronic disease in 10% of infected adults and 90% of infected children, and can eventually lead to liver failure or cancer. Credit: theasis/Getty Images.
Hepatitis B virus spreads through contact with blood or sexual activity and may be transmitted from mother to child during birth. It can cause both acute and chronic disease. About 10% of infected adults and 90% of infected children develop chronic hepatitis, that eventually can evolve into liver failure or cancer. Despite a highly effective vaccine, the chronic disease affects about 300 million people in the world, most of whom were infected before the introduction of the vaccine, or in areas where it isn’t available. Current therapies against the chronic infection are lifelong antiviral treatments that can only moderate the risk of liver damage.
In 2019, researchers at IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele University, in Milan discovered2 that specific immune cells called CD8 positive lymphocytes T fight the virus during the acute infection, but stop working properly when the infection becomes chronic.
They also discovered that interleukin-2, a signalling molecule of the immune system, can reverse the process and prompt CD8 cells back to fight the virus. “But interleukin-2 also triggers other immune cells linked to systemic toxicity and immunosuppressive activity, so we cannot use it as a safe therapy for hepatitis B,” says Matteo Iannacone, head of the Immunology, Transplantation and Infectious Diseases at San Raffaele Scientific Institute, and senior author of the paper.
Now the research team, in collaboration with Asher Biotherapeutics, in the United States, conjugated interleukin-2 to an antibody specifically targeting CD8 positive lymphocytes T. The new drug reinvigorates the cells’ antiviral activity while avoiding activation of other lymphocytes, reducing toxicity and immunosuppressive effects, making it a potential option for chronic hepatitis B. “Asher is carrying out a phase 1 clinical trial of the same drug on cancer patients and we are waiting to know the results on safety before planning clinical trials for chronic hepatitis,” says Iannacone.
