ArticleJournal of thrombosis and haemostasis : JTH2011
Induction of tolerance to factor VIII by transient co-administration with rapamycin.
Article in Journal of thrombosis and haemostasis : JTH, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05920512 (PLA General Hospital), which is not on this map. Cited by 66 papers.
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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.
PLA General Hospital
Who cites it
66 citing papers in PubMed, 88 citations in OpenAlex.
- Safety of Intradiaphragmatic Delivery of Adeno-Associated Virus-Mediated Alpha-Glucosidase (rAAV1-CMV-hGAA) Gene Therapy in Children Affected by Pompe Disease.Human gene therapy. Clinical development · 2017Trial
- B-Cell depletion and immunomodulation before initiation of enzyme replacement therapy blocks the immune response to acid alpha-glucosidase in infantile-onset Pompe disease.The Journal of pediatrics · 2013Trial
- Miniaturized subcutaneous cellular implants for sustained therapeutic protein delivery in resource-limited settings.bioRxiv : the preprint server for biology · 2026Article
- Identification of alterations of immunometabolism associated with Pompe disease.Cellular and molecular life sciences : CMLS · 2026Article
- Enhancing AAV9-UFμDys1 Gene Therapy Efficacy Through Immunosuppression in Mice with Pre-Existing Immunity and Enabling Redosing Strategies for Duchenne Muscular Dystrophy.Human gene therapy · 2026Article
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 2025Article
- Transplanted gene-modified placental cells boost FVIII activity in pediatric sheep without eliciting immunity, toxicity, or adverse events.Frontiers in immunology · 2025Article
- Liver-directed AAV gene therapy normalizes disease symptoms and provides cross-correction in a model of lysosomal acid lipase deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- 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
- A comprehensive overview of tolerogenic vaccine adjuvants and their modes of action.Frontiers in immunology · 2024Review
- Adeno-associated virus-vectored delivery of HIV biologics: the promise of a "single-shot" functional cure for HIV infection.Journal of virus eradication · 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
- Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1+ Tregs.The Journal of clinical investigation · 2022Article
- Antigen-specific immunotherapy with apitopes suppresses generation of FVIII inhibitor antibodies in HLA-transgenic mice.Blood advances · 2022Article
- Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics.Frontiers in immunology · 2021Review
- Role of Small Intestine and Gut Microbiome in Plant-Based Oral Tolerance for Hemophilia.Frontiers in immunology · 2020Article
- B Cell Depletion Eliminates FVIII Memory B Cells and Enhances AAV8-coF8 Immune Tolerance Induction When Combined With Rapamycin.Frontiers in immunology · 2020Article
- Development of ImmTOR Tolerogenic Nanoparticles for the Mitigation of Anti-drug Antibodies.Frontiers in immunology · 2020Review
- A Treg-Selective IL-2 Mutein Prevents the Formation of Factor VIII Inhibitors in Hemophilia Mice Treated With Factor VIII Gene Therapy.Frontiers in immunology · 2020Article
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFormation of inhibitory antibodies is a frequent and serious complication of factor (F) VIII replacement therapy for the X-linked bleeding disorder hemophilia A. Similarly, hemophilia A mice develop high-titer inhibitors to recombinant human FVIII after a few intravenous injections.
objectiveUsing the murine model, the study sought to develop a short regimen capable of inducing tolerance to FVIII.
methodsA 1-month immunomodulatory protocol, consisting of FVIII administration combined with oral delivery of rapamycin, was developed.
resultsThe protocol effectively prevented formation of inhibitors to FVIII upon subsequent intravenous treatment (weekly for 3.5 months). Control mice formed high-titer inhibitors and had CD4(+) T effector cell responses characterized by expression of IL-2, IL-4 and IL-6. Tolerized mice instead had a CD4(+)CD25(+)FoxP3(+) T cell response to FVIII that suppressed antibody formation upon adoptive transfer, indicating a shift from Th2 to Treg if FVIII antigen was introduced to T cells during inhibition with rapamycin. CD4(+) T cells from tolerized mice also expressed TGF-β1 and CTLA4, but not IL-10. The presence of FVIII antigen during the time of rapamycin administration was required for specific tolerance induction.
conclusionsThe study shows that a prophylactic immune tolerance protocol for FVIII can be developed using rapamycin, a drug that is already widely in clinical application. Immune suppression with rapamycin was mild and highly transient, as the mice regained immune competence within a few weeks.
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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.