T-cell therapy successfully cured chronic hepatitis B virus (HBV) in a mouse model, representing the first time that researchers have succeeded in fully controlling the virus, according to a new study published in the Journal of Clinical Proceedings.
Chronic HBV affects more than 260 million individuals worldwide, according to the World Health Organization. Although vaccinations can prevent new HBV infections, there is currently no cure for chronic carriers of the virus. Available therapy regimens can suppress viral reaction but are unable to eliminate the virus completely, indicating the need for more therapeutic options.
For the study, the researchers used a new T-cell therapy specifically designed to fight HBV infection and HBV-associated liver cancer, testing the immune cells in a humanized mouse model.
“Restoring a potent T-cell response by adoptive T cell therapy is an interesting therapeutic option,” the researchers wrote in the study. “The concept of transferring adaptive immunity to control HBV has already been applied successfully in patients with CHB who underwent stem cell transplantation and received bone marrow from HBV-immune donors.”
According to the researchers, strong T-cell responses can become detectable if patients are able to keep the virus under control by themselves.
“The obvious answer is therefore to use virus-specific T cells to make up for this deficit,” lead study author Karin Wisskirchen, PhD, said in a press release about the study.
According to Wisskirchen, the genetic information for HBV-specific T-cell receptors can be introduced into T cells in the laboratory from the blood of patients with chronic HBV, which leads to the formation of new, active T cells.
In the mouse model, a single dose of receptor-modified T-cells was sufficient to control the virus in the liver. However, the absence of adaptive immune responses eventually led to viral rebound in the mice. To combat this, the researchers administered an experimental drug Myrcludex B to prevent the virus from infecting healthy liver cells again when the T-cells had stopped circulating, achieving long-term control in the mice. Myrcludex B is an inhibitor of the entry of HB viruses into liver cells, according to the study. It is currently in a phase 3 clinical trial for the treatment of chronic hepatitis D.
“The promising results of this study will help us to further investigate the potential of T-cell therapy and go ahead with clinical trials along with our partners,” Ulrike Protzer, MD, director of the Institute of Virology at Helmholtz Zentrum München and at the Technical University of Munich, said in the release. “We are thus taking a decisive step towards establishing this form of personalized medicine.”
Wisskirchen K, Kah J, Malo A, et al. T cell receptor grafting allows virological control of hepatitis B virus infection. The Journal of Clinical Investigation.
2019. Doi: 10.1172/JCI120228
Checkmate for hepatitis B viruses in the liver [news release]. https://www.helmholtz-muenchen.de/en/press-media/press-releases/all-press-releases/press-release/article/46390/index.html
. Accessed June 11, 2019.