ArticleMolecular therapy. Methods & clinical development2017
In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy.
Article in Molecular therapy. Methods & clinical development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Next-generation T cell engagers for cancer and autoimmune diseases.Frontiers in immunology · 2026Review
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- Chimeric PRR T-cell-engager targeting cell surface β-1,3-glucan for invasive candidiasis.PLoS pathogens · 2025Article
- The role of γδ T cells in flavivirus infections: Insights into immune defense and therapeutic opportunities.PLoS neglected tropical diseases · 2025Review
- Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases.Cellular & molecular immunology · 2024Review
- Changes in the IL-18, IL-22, and T lymphocyte subset levels in patients with hepatitis B-related liver cirrhosis and their predictive values for hepatorenal syndrome.American journal of translational research · 2023Article
- Protective Effect of the Polysaccharides fromFoods (Basel, Switzerland) · 2022Article
- Activation of distinct antiviral T-cell immunity: A comparison of bi- and trispecific T-cell engager antibodies with a chimeric antigen receptor targeting HBV envelope proteins.Frontiers in immunology · 2022Article
- Bioassay Development for Bispecific Antibodies-Challenges and Opportunities.International journal of molecular sciences · 2021Review
- Cre/LoxP-HBV plasmids generating recombinant covalently closed circular DNA genome upon transfection.Virus research · 2021Article
- The Contribution of Liver Sinusoidal Endothelial Cells to Clearance of Therapeutic Antibody.Frontiers in physiology · 2021Review
- The roles of the glucagon-like peptide-2 and the serum TGF-β1 levels in the intestinal barrier and immune functions in rats with obstructive jaundice.American journal of translational research · 2021Article
- Quantum leap of monoclonal antibody (mAb) discovery and development in the COVID-19 era.Seminars in immunology · 2020Review
- Restoring, releasing or replacing adaptive immunity in chronic hepatitis B.Nature reviews. Gastroenterology & hepatology · 2019Review
- Bispecific antibodies: a mechanistic review of the pipeline.Nature reviews. Drug discovery · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Current therapies against hepatitis B virus (HBV) do not reliably cure chronic infection, necessitating new therapeutic approaches. The T cell response can clear HBV during acute infection, and the adoptive transfer of antiviral T cells during bone marrow transplantation can cure patients of chronic HBV infection. To redirect T cells to HBV-infected hepatocytes, we delivered plasmids encoding bispecific antibodies directed against the viral surface antigen (HBsAg) and CD3, expressed on almost all T cells, directly into the liver using hydrodynamic tail vein injection. We found a significant reduction in HBV-driven reporter gene expression (184-fold) in a mouse model of acute infection, which was 30-fold lower than an antibody only recognizing HBsAg. While bispecific antibodies triggered, in part, antigen-independent T cell activation, antibody production within hepatocytes was non-cytotoxic. We next tested the bispecific antibodies in a different HBV mouse model, which closely mimics the transcriptional template for HBV, covalently closed circular DNA (cccDNA). We found that the antiviral effect was noncytopathic, mediating a 495-fold reduction in HBsAg levels at day 4. At day 33, bispecific antibody-treated mice exhibited 35-fold higher host HBsAg immunoglobulin G (IgG) antibody production versus untreated groups. Thus, gene therapy with HBsAg/CD3-bispecific antibodies represents a promising therapeutic strategy for patients with HBV.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.