Bioengineering Meets Hepatitis B: Researchers Design Promising Novel Therapeutic Candidates
Researchers have designed antibodies as novel therapeutic candidates for the treatment of chronic hepatitis B and hepatocellular carcinoma. Their study in human cell cultures and in living mice showed the elimination of antigen-positive cells and reduction of tumor growth. The scientists now have teamed-up with industry partners to continue to develop this approach for clinical application and to initiate clinical studies.
Patients with chronic hepatitis B fail to mount an adequate immune response allowing the virus to persist. This results in around 260 million chronic carriers of the virus, more than three percent of the world's population. Consequently, 880,000 people worldwide die of liver failure or hepatocellular carcinoma each year. Available therapies inhibit viral replication, but rarely cure chronic infections.
Supporting the immune system to do its job
Researchers at Helmholtz Zentrum München and the Technical University of Munich focus on finding ways to cure chronic hepatitis B virus infections by stimulating the patient’s immune response. Their latest study features an immunotherapeutic tool, which has evolved in the recent years: Bispecific antibodies that serve as T-cell engagers. As the name says, these antibodies engage T-cells, a specific type of blood cell that plays a major role in our adaptive immune system, and redirect them towards infected cells. Thus, the bispecific T-cell engager antibodies connect infected cells with immune cells, and in turn boost T-cell activity to kill the infected cells. “We used this tool and re-designed it for our purposes,” says Oliver Quitt. “We engineered antibodies with the goal to induce antiviral immunity in patients with a chronic hepatitis B infection”.
Therapeutic candidate for chronic hepatitis B and hepatocellular carcinoma
Their study in mice already showed promising results. “Our newly designed antibodies successfully connected liver cells infected with the hepatitis B virus with immune cells. Moreover, the antibodies attracted the T-cells directly to hepatitis B associated tumors and reduced their growth,” explains Shanshan Luo.
Study leader Ulrike Protzer sees great potential in these findings: “Our study demonstrates that the administration of bispecific T-cell engager antibodies is a promising approach for the treatment of chronic hepatitis B and hepatocellular carcinoma. To push this approach forward, we recently filed a research agreement with the biotechnology company SCG Cell Therapy. Our goal is to further develop this novel technology and facilitate its clinical application within the next years”.
About the people
Ulrike Protzer is full professor for virology and leads the Institute of Virology, which belongs to Helmholtz Zentrum München and the Technical University of Munich. Within her team, Oliver Quitt and Shanshan Luo conducted this research as PhD student and PostDoc, respectively. Ulrike Protzer is a member of the German Center for Infection Research (DZIF) and spokesperson of its Thematic Translational Unit Hepatitis.
Quitt, Luo et al., 2021: <link www.journal-of-hepatology.eu/article/S0168-8278(21)00443-8/fulltext - extern>T cell engager antibodies enable T cells to control HBV infection and to target HBsAg-positive hepatoma in mice.</link> Journal of Hepatology, DOI: 10.1016/j.jhep.2021.06.022