Current liver research: Promising Immunotherapy with transiently activated T-cells for patients suffering from chronic hepatitis B virus infection

1. August 2017

In patients chronically infected with the hepatitis B virus, a way to gain control over the virus and to strengthen the immunity of the patients against the virus has to be found. The scientists around Prof. Maura Dandri, head of the subproject A5, succeed in cooperation with Prof. Bertoletti in Singapur, for the first time in synthesizing such T cells, which transiently, for a period of 96 hours, assess their antiviral and pathogenetic activity in vitro and in HBV infected human liver chimeric mice.

By using electroporation, a specific method to transfer mRNA, the T-cells are expressing HBV-specific TCRs. To date, the testing of the method with human T cells directed against the HB virus has not been permitted in humans because of safety concerns. These concerns are mainly due to uncontrolled proliferation of cells in the body.

“We have shown that the HBV-specific T cells are capable of leading to cell death of liver cells carrying the hepatitis B virus,” explains Prof. Maura Dandri. In the humanized mouse model, injections of the specific T cells, expressing the HBV-specific T-cell receptors, could even show a strong reduction in the viral infection, whereas the T-cells, carrying a receptor recognizing the hepatitis C virus, did not change or reduce the HBV infection.

“We were able to show that the so-called T-cell transfer did not lead to any inflammatory reactions in mice that were not infected with HBV,” explains Prof. Dandri. Overall, the data from this study support the assumption that the synthesized T cells carrying the receptor against HBV can be successfully used and further be tested in patients suffering from a chronic HBV infection.

Publication
h4(pub). Kah J, Koh S, Volz T, Ceccarello E, Allweiss L, Lütgehetmann M, Bertoletti A, Dandri M

Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection
J Clin Invest. 2017 Jul 24. pii: 93024. doi: 10.1172/JCI93024. [Epub ahead of print]