ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Oral Tolerance Induction in Hemophilia B Dogs Fed with Transplastomic Lettuce.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
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- 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
- 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
- Delivery of biologics: Topical administration.Biomaterials · 2023Review
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- 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
- Distinct functions and transcriptional signatures in orally induced regulatory T cell populations.Frontiers in immunology · 2023Article
- Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.Cellular immunology · 2022Review
- Article
- Contributions of the international plant science community to the fight against human infectious diseases - part 1: epidemic and pandemic diseases.Plant biotechnology journal · 2021Review
- 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
- Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy?Gene therapy · 2021Review
- Oral delivery of therapeutic proteins bioencapsulated in plant cells: preclinical and clinical advances.Current opinion in colloid & interface science · 2021Article
- Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Anti-drug antibodies in hemophilia patients substantially complicate treatment. Their elimination through immune tolerance induction (ITI) protocols poses enormous costs, and ITI is often ineffective for factor IX (FIX) inhibitors. Moreover, there is no prophylactic ITI protocol to prevent anti-drug antibody (ADA) formation. Using general immune suppression is problematic. To address this urgent unmet medical need, we delivered antigen bioencapsulated in plant cells to hemophilia B dogs. Commercial-scale production of CTB-FIX fusion expressed in lettuce chloroplasts was done in a hydroponic facility. CTB-FIX (∼1 mg/g) in lyophilized cells was stable with proper folding, disulfide bonds, and pentamer assembly after 30-month storage at ambient temperature. Robust suppression of immunoglobulin G (IgG)/inhibitor and IgE formation against intravenous FIX was observed in three of four hemophilia B dogs fed with lyophilized lettuce cells expressing CTB-FIX. No side effects were detected after feeding CTB-FIX-lyophilized plant cells for >300 days. Coagulation times were markedly shortened by intravenous FIX in orally tolerized treated dogs, in contrast to control dogs that formed high-titer antibodies to FIX. Commercial-scale production, stability, prolonged storage of lyophilized cells, and efficacy in tolerance induction in a large, non-rodent model of human disease offer a novel concept for oral tolerance and low-cost production and delivery of biopharmaceuticals.
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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.