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Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
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Chimeric antigen receptors of HBV envelope proteins inhibit hepatitis B surface antigen secretion
Yang Wang1, Qiqi Li1, Cheng Li1
1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontier Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Gut
|November 16, 2023
Summary
New chimeric antigen receptors (CARs) targeting hepatitis B virus (HBV) envelope proteins effectively reduce HBsAg. These novel CARs offer a promising strategy for achieving sustained HBsAg loss in chronic hepatitis B patients.
Area of Science:
- Hepatology
- Virology
- Immunotherapy
Background:
- Chronic hepatitis B (CHB) poses a significant risk for liver cirrhosis and cancer.
- Hepatitis B surface antigen (HBsAg) is crucial in CHB pathogenesis, and its loss signifies a cure.
- Current drugs rarely achieve sustained HBsAg loss, necessitating novel therapeutic strategies.
Purpose of the Study:
- To develop and evaluate chimeric antigen receptors (CARs) targeting HBV envelope proteins for HBsAg reduction.
- To investigate the impact of CARs on HBsAg secretion, HBV infection, and underlying mechanisms.
Main Methods:
- Development of CARs using single-chain variable fragments (scFvs) targeting HBV large and small envelope proteins.
- In vitro studies using cell culture models to assess CARs' effects on HBV infection and HBsAg secretion.
- In vivo studies using HBV mouse models to evaluate the efficacy of CARs in reducing serum HBsAg.
Main Results:
- CARs, particularly G12-scFv-Fc and G12-CAR-Fc, significantly suppressed serum HBsAg in HBV mouse models (up to 130-fold).
- The inhibitory effect of CARs on HBsAg lasted for at least 8 weeks post-delivery via adeno-associated virus vector.
- CARs demonstrated direct antiviral activity by blocking HBV infection, virion secretion, and HBsAg release, primarily by arresting HBV envelope proteins in the endoplasmic reticulum.
Conclusions:
- Chimeric antigen receptors (CARs) exhibit direct antiviral activity against HBV.
- Fc-fused G12-scFv and G12-CARs represent a novel therapeutic approach for reducing circulating HBsAg in CHB.
- These findings pave the way for new strategies aimed at achieving sustained HBsAg loss and potentially curing CHB.
