ArticleBlood2014
Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Pooled it
- Plant-Based Systems for Producing Therapeutic Proteins: Current Status and Future Prospects.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Engineering Marker-Free Lettuce Chloroplast Genome to Express Functional Glucagon-Like Peptide-1 Receptor Agonists Exenatide and Lixisenatide.Plant biotechnology journal · 2026Article
- Applying Fc-fusion proteins to tolerize perinatally and block inhibitor formation.Haematologica · 2025Article
- Progress and Challenges in the Treatment of Fabry Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance.Folia microbiologica · 2024Article
- Green Biologics: Harnessing the Power of Plants to Produce Pharmaceuticals.International journal of molecular sciences · 2023Review
- Factor IX administration in the skin primes inhibitor formation and sensitizes hemophilia B mice to systemic factor IX administration.Research and practice in thrombosis and haemostasis · 2023Article
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- Plant-made pharmaceuticals: exploring studies for the production of recombinant protein in plants and assessing challenges ahead.Plant biotechnology reports · 2023Review
- Distinct functions and transcriptional signatures in orally induced regulatory T cell populations.Frontiers in immunology · 2023Article
- IL-15 blockade and rapamycin rescue multifactorial loss of factor VIII from AAV-transduced hepatocytes in hemophilia A mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.Cellular immunology · 2022Review
- Article
- The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.Frontiers in immunology · 2022Review
- Preclinical development of plant-based oral immune modulatory therapy for haemophilia B.Plant biotechnology journal · 2021Article
- Contributions of the international plant science community to the fight against infectious diseases in humans-part 2: Affordable drugs in edible plants for endemic and re-emerging diseases.Plant biotechnology journal · 2021Review
- Oral delivery of therapeutic proteins bioencapsulated in plant cells: preclinical and clinical advances.Current opinion in colloid & interface science · 2021Article
- Green giant-a tiny chloroplast genome with mighty power to produce high-value proteins: history and phylogeny.Plant biotechnology journal · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hemophilia A is the X-linked bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). To address serious complications of inhibitory antibody formation in current replacement therapy, we created tobacco transplastomic lines expressing FVIII antigens, heavy chain (HC) and C2, fused with the transmucosal carrier, cholera toxin B subunit. Cholera toxin B-HC and cholera toxin B-C2 fusion proteins expressed up to 80 or 370 µg/g in fresh leaves, assembled into pentameric forms, and bound to GM1 receptors. Protection of FVIII antigen through bioencapsulation in plant cells and oral delivery to the gut immune system was confirmed by immunostaining. Feeding of HC/C2 mixture substantially suppressed T helper cell responses and inhibitor formation against FVIII in mice of 2 different strain backgrounds with hemophilia A. Prolonged oral delivery was required to control inhibitor formation long-term. Substantial reduction of inhibitor titers in preimmune mice demonstrated that the protocol could also reverse inhibitor formation. Gene expression and flow cytometry analyses showed upregulation of immune suppressive cytokines (transforming growth factor β and interleukin 10). Adoptive transfer experiments confirmed an active suppression mechanism and revealed induction of CD4(+)CD25(+) and CD4(+)CD25(-) T cells that potently suppressed anti-FVIII formation. In sum, these data support plant cell-based oral tolerance for suppression of inhibitor formation against FVIII.
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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.