ArticleGut2018
Humanisation of a claudin-1-specific monoclonal antibody for clinical prevention and cure of HCV infection without escape.
Article in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Introducing fluorescence guided surgery into orthopedic oncology: A systematic review of candidate protein targets for Ewing sarcoma.Journal of surgical oncology · 2018Pooled it
- Structure-forward targeting of claudins with synthetic binders.FEBS letters · 2026Review
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- A Synopsis of Hepatitis C Virus Treatments and Future Perspectives.Current issues in molecular biology · 2023Review
- Review
- Tight Junctions, the Key Factor in Virus-Related Disease.Pathogens (Basel, Switzerland) · 2022Review
- Entry Inhibitors of Hepatitis C Virus.Advances in experimental medicine and biology · 2022Article
- Targeting claudins in cancer: diagnosis, prognosis and therapy.American journal of cancer research · 2021Review
- Hepatitis C virus infection and tight junction proteins: The ties that bind.Biochimica et biophysica acta. Biomembranes · 2020Review
- Characterisation of endogenous Claudin-1 expression, motility and susceptibility to hepatitis C virus in CRISPR knock-in cells.Biology of the cell · 2020Article
- Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process.International journal of molecular sciences · 2020Review
- Tight Junction Proteins and the Biology of Hepatobiliary Disease.International journal of molecular sciences · 2020Review
- Role of Claudin Proteins in Regulating Cancer Stem Cells and Chemoresistance-Potential Implication in Disease Prognosis and Therapy.International journal of molecular sciences · 2019Review
- Interferon-Induced Transmembrane Proteins Mediate Viral Evasion in Acute and Chronic Hepatitis C Virus Infection.Hepatology (Baltimore, Md.) · 2019Article
- Use of ModifiedInternational journal of molecular sciences · 2019Article
- Review
- Article
- Review
- In vivo combination of human anti-envelope glycoprotein E2 and -Claudin-1 monoclonal antibodies for prevention of hepatitis C virus infection.Antiviral research · 2019Article
- Monoclonal Antibodies against Occludin Completely Prevented Hepatitis C Virus Infection in a Mouse Model.Journal of virology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHCV infection is a leading cause of chronic liver disease and a major indication for liver transplantation. Although direct-acting antivirals (DAAs) have much improved the treatment of chronic HCV infection, alternative strategies are needed for patients with treatment failure. As an essential HCV entry factor, the tight junction protein claudin-1 (CLDN1) is a promising antiviral target. However, genotype-dependent escape via CLDN6 and CLDN9 has been described in some cell lines as a possible limitation facing CLDN1-targeted therapies. Here, we evaluated the clinical potential of therapeutic strategies targeting CLDN1.
designWe generated a humanised anti-CLDN1 monoclonal antibody (mAb) (H3L3) suitable for clinical development and characterised its anti-HCV activity using cell culture models, a large panel of primary human hepatocytes (PHH) from 12 different donors, and human liver chimeric mice.
resultsH3L3 pan-genotypically inhibited HCV pseudoparticle entry into PHH, irrespective of donor. Escape was likely precluded by low surface expression of CLDN6 and CLDN9 on PHH. Co-treatment of a panel of PHH with a CLDN6-specific mAb did not enhance the antiviral effect of H3L3, confirming that CLDN6 does not function as an entry factor in PHH from multiple donors. H3L3 also inhibited DAA-resistant strains of HCV and synergised with current DAAs. Finally, H3L3 cured persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.
conclusionsOverall, these findings underscore the clinical potential of CLDN1-targeted therapies and describe the functional characterisation of a humanised anti-CLDN1 antibody suitable for further clinical development to complement existing therapeutic strategies for HCV.
Indexed as
Identifiers
What OpenQuestion holds
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.