ArticleJournal of hepatology2018
Anti-HBV response to toll-like receptor 7 agonist GS-9620 is associated with intrahepatic aggregates of T cells and B cells.
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators.Hepatology (Baltimore, Md.) · 2021Trial
- NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis.Hepatology (Baltimore, Md.) · 2020Trial
- Innate immune recognition and evasion strategies of hepatitis B virus: from DNA to RNA and viral proteins.Frontiers in immunology · 2026Review
- Dissecting the Efficacy and Immunogenicity of TLR7 Agonist-Antibody Conjugates through the Lens of Fc Effector Function, Conjugation Strategies, and Linker Cleavability.Journal of medicinal chemistry · 2025Article
- Anti-PD-L1-IFN-α-adjuvanted HBsAg vaccine overcomes HBV immune tolerance through targeting both DCs and macrophages.JCI insight · 2025Article
- Antiviral and immune modulatory activities of STING agonists in a mouse model of persistent hepatitis B virus infection.PLoS pathogens · 2025Article
- Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers.Immunological reviews · 2025Review
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- Toll-like receptor agonists promote the formation of tertiary lymphoid structure and improve anti-glioma immunity.Neuro-oncology · 2025Article
- Immunomodulation and entry inhibition: selgantolimod's double punch against hepatitis B virus.Gut · 2024Article
- Article
- Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade.bioRxiv : the preprint server for biology · 2024Article
- Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2024Review
- Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade.Frontiers in immunology · 2024Article
- HBV Vaccines: Advances and Development.Vaccines · 2023Review
- Recent Insights into the Role of B Cells in Chronic Hepatitis B and C Infections.Pathogens (Basel, Switzerland) · 2023Review
- Targeting toll-like receptor 7/8 for immunotherapy: recent advances and prospectives.Biomarker research · 2022Review
- Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV.JHEP reports : innovation in hepatology · 2022Review
- Novel Molecular Therapeutics Targeting Signaling Pathway to Control Hepatitis B Viral Infection.Frontiers in cellular and infection microbiology · 2022Review
- Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection.JHEP reports : innovation in hepatology · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsGS-9620, an oral agonist of toll-like receptor 7, is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the chimpanzee and woodchuck models of CHB. Herein, we investigated the immunomodulatory mechanisms underlying these antiviral effects.
methodsArchived liver biopsies and paired peripheral blood mononuclear cell samples from a previous chimpanzee study were analyzed by RNA sequencing, quantitative reverse transcription PCR, immunohistochemistry (IHC) and in situ hybridization (ISH).
resultsGS-9620 treatment of CHB chimpanzees induced an intrahepatic transcriptional profile significantly enriched with genes associated with hepatitis B virus (HBV) clearance in acutely infected chimpanzees. Type I and II interferon, CD8
conclusionThe antiviral response to GS-9620 treatment in CHB chimpanzees was associated with an intrahepatic interferon response and formation of lymphoid aggregates in the liver. Our data indicate these intrahepatic structures are not fully differentiated follicles containing germinal center reactions. However, the temporal correlation between development of these T and B cell aggregates and the antiviral response to treatment suggests they play a role in promoting an effective immune response against HBV. LAY SUMMARY: New therapies to treat chronic hepatitis B (CHB) are urgently needed. In this study we performed a retrospective analysis of liver and blood samples from a chimpanzee model of CHB to help understand how GS-9620, a drug in clinical trials, suppressed hepatitis B virus (HBV). We found that the antiviral response to GS-9620 was associated with accumulation of immune cells in the liver that can either kill cells infected with HBV or can produce antibodies that may prevent HBV from infecting new liver cells. These findings have important implications for how GS-9620 may be used in patients and may also help guide the development of new therapies to treat chronic HBV infection.
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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.