ArticleBlood2016
The immunogenicity of platelet-derived FVIII in hemophilia A mice with or without preexisting anti-FVIII immunity.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- FVIII-containing platelets modulate immune responses and attenuate inhibitor development in hemophilia A mice.Haematologica · 2026Article
- Impact of antiplatelet therapy on the hemostatic efficacy of platelet-targeted FVIII gene therapy in hemophilia A mice.Blood advances · 2026Article
- Chemokine CXCL13 facilitates anti-FVIII inhibitory antibody development in hemophilia A patients and murine models.International immunopharmacology · 2024Article
- Evaluating clinically translatable conditioning for platelet gene therapy in murine hemophilia A with inhibitors.Journal of thrombosis and haemostasis : JTH · 2024Article
- Platelet-targeted gene therapy induces immune tolerance in hemophilia and beyond.Journal of thrombosis and haemostasis : JTH · 2024Review
- Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets.Scientific reports · 2023Article
- Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells.Journal of thrombosis and haemostasis : JTH · 2023Article
- Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression.Research (Washington, D.C.) · 2023Article
- Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.Frontiers in immunology · 2022Review
- Thromboelastometry assessment of hemostatic properties in various murine models with coagulopathy and the effect of factor VIII therapeutics.Journal of thrombosis and haemostasis : JTH · 2021Article
- Platelet gene therapy induces robust immune tolerance even in a primed model via peripheral clonal deletion of antigen-specific T cells.Molecular therapy. Nucleic acids · 2021Article
- Activated factor X targeted stored in platelets as an effective gene therapy strategy for both hemophilia A and B.Clinical and translational medicine · 2021Article
- Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential.Drug delivery and translational research · 2021Review
- In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy.Journal of cellular physiology · 2021Article
- Maternal microchimerism protects hemophilia A patients from inhibitor development.Blood advances · 2020Article
- The severe spontaneous bleeding phenotype in a novel hemophilia A rat model is rescued by platelet FVIII expression.Blood advances · 2020Article
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
- Induction of activated T follicular helper cells is critical for anti-FVIII inhibitor development in hemophilia A mice.Blood advances · 2019Article
- Platelet-Targeted Gene Therapy for Hemophilia.Molecular therapy. Methods & clinical development · 2018Review
- Immune tolerance induced by platelet-targeted factor VIII gene therapy in hemophilia A mice is CD4 T cell mediated.Journal of thrombosis and haemostasis : JTH · 2017Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Evidence shows that factor VIII (FVIII) ectopically expressed in platelets (2bF8) is therapeutic in FVIII(null) mice even with anti-FVIII inhibitory antibodies (inhibitors). If current efforts to generate platelets in vitro succeed, genetically manipulated platelets containing FVIII may be used therapeutically in hemophilia A patients with inhibitors. One important concern is the immunogenicity of platelet-derived FVIII. To address this concern, we infused 2bF8 transgenic (2bF8(Tg)) platelets into naïve FVIII(null) mice weekly for 8 weeks. No anti-FVIII antibodies were detected in the infused animals during the study course. We then explored whether platelet-derived FVIII is immunogenic in FVIII(null) mice with inhibitors. The 2bF8(Tg) platelets were transfused into rhF8-primed FVIII(null) mice, resulting in no augmentation of anti-FVIII antibodies. To investigate whether preconditioning affects the immune response, animals were sublethally irradiated and subsequently transfused with 2bF8(Tg) platelets. No anti-FVIII antibodies were detected in the recipients after platelet infusions. Following further challenge with rhF8, the inhibitor titer in this group was significantly lower than in naïve FVIII(null) mice utilizing the same immunization protocol. Thus, our data demonstrate that infusion of platelets containing FVIII triggers neither primary nor memory anti-FVIII immune response in FVIII(null) mice and that sublethal irradiation plus 2bF8(Tg) platelet infusion suppresses anti-FVIII immune response in FVIII(null) mice.
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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.