ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Immune tolerance induction to factor IX through B cell gene transfer: TLR9 signaling delineates between tolerogenic and immunogenic B cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 31 citations in OpenAlex.
- B cell-activating factor modulates the factor VIII immune response in hemophilia A.The Journal of clinical investigation · 2021Trial
- CAR T cell therapy beyond cancer: current status, challenges and future prospects.Signal transduction and targeted therapy · 2026Review
- Enhanced B cell electroporation efficiency via inhibition of DNA-induced apoptosis and pyroptosis with pan-caspase inhibitor.Molecular therapy. Methods & clinical development · 2025Article
- Engineering B cells to treat and study human disease.Nature biotechnology · 2025Review
- Envelope protein-specific B cell receptors direct lentiviral vector tropism in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.Molecular therapy. Methods & clinical development · 2024Article
- Genome edited B cells: a new frontier in immune cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Engineering Tolerance toward Allogeneic CAR-T Cells by Regulation of MHC Surface Expression with Human Herpes Virus-8 Proteins.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer.Cellular immunology · 2019Article
- Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes.Molecular therapy. Methods & clinical development · 2019Review
- Molecular Design, Optimization, and Genomic Integration of Chimeric B Cell Receptors in Murine B Cells.Frontiers in immunology · 2019Article
- Tolerance induction in hemophilia: innovation and accomplishments.Current opinion in hematology · 2018Review
- Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells.Molecular therapy. Methods & clinical development · 2017Article
- Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A.Frontiers in immunology · 2017Review
- Gene therapy for immune tolerance induction in hemophilia with inhibitors.Journal of thrombosis and haemostasis : JTH · 2016Review
- In vivo induction of regulatory T cells for immune tolerance in hemophilia.Cellular immunology · 2016Review
- Clinical development of gene therapy: results and lessons from recent successes.Molecular therapy. Methods & clinical development · 2016Review
- Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B.Biomaterials · 2015Article
- Synergistic Efficacy from Gene Therapy with Coreceptor Blockade and a β2-Agonist in Murine Pompe Disease.Human gene therapy · 2015Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A subset of patients with severe hemophilia B, the X-linked bleeding disorder resulting from absence of coagulation factor IX (FIX), develop pathogenic antibody responses during replacement therapy. These inhibitors block standard therapy and are often associated with anaphylactic reactions to FIX. Established clinical immune tolerance induction protocols often fail for FIX inhibitors. In a murine model of this immune complication, retrovirally transduced primary B cells expressing FIX antigen fused with immunoglobulin-G heavy chain prevented antibody formation to FIX and was also highly effective in desensitizing animals with preexisting response. In contrast, transplant of B cells that received the identical expression cassette via nucleofection of plasmid vector substantially heightened antibody formation against FIX, a response that could be blocked by toll-like receptor 9 (TLR9) inhibition. While innate responses to TLR4 activation or to retrovirus were minimal in B cells, plasmid DNA activated TLR9, resulting in CpG-dependent NF-κB activation/IL-6 expression and adaptor protein 3 dependent, CpG-independent induction of IFN-I. Neither response was seen in TLR9-deficient B cells. Therefore, TLR9 signaling in B cells, in particular in response to plasmid vector, is highly immunogenic and has to be avoided in design of tolerance protocols.
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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.