ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents anti-factor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 48 citations in OpenAlex.
- Immune System-Related Genetic Risk Factors for Inhibitory Antibody Development in Patients With Hemophilia: Reviewing an Old Problem From a New Perspective-A Narrative Review.Health science reports · 2025Article
- Role of FoxP3Human gene therapy · 2024Review
- Induction of long-term tolerance to a specific antigen using anti-CD3 lipid nanoparticles following gene therapy.Molecular therapy. Nucleic acids · 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
- Transcutaneous ultrasound-mediated gene delivery into canine livers achieves therapeutic levels of factor VIII expression.Blood advances · 2022Article
- Ultrasound-mediated gene delivery of factor VIII plasmids for hemophilia A gene therapy in mice.Molecular therapy. Nucleic acids · 2022Article
- IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25eLife · 2021Article
- In Vivo Expansion of Antigen-Specific Regulatory T Cells through Staggered Fc.IL-2 Mutein Dosing and Antigen-Specific Immunotherapy.ImmunoHorizons · 2021Article
- CD4Cellular immunology · 2020Article
- Antigen-specific in vitro expansion of factor VIII-specific regulatory T cells induces tolerance in hemophilia A mice.Journal of thrombosis and haemostasis : JTH · 2020Article
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies for Hemophilia A Patients.International journal of molecular and cellular medicine · 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
- Reprogrammed CD4Frontiers in immunology · 2019Article
- Platelet Gene Therapy Promotes Targeted Peripheral Tolerance by Clonal Deletion and Induction of Antigen-Specific Regulatory T Cells.Frontiers in immunology · 2018Article
- 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
- Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A.Frontiers in immunology · 2017Review
- In vivo induction of regulatory T cells for immune tolerance in hemophilia.Cellular immunology · 2016Review
- Strategies to target long-lived plasma cells for treating hemophilia A inhibitors.Cellular immunology · 2016Article
- IL-2/α-IL-2 Complex Treatment Cannot Be Substituted for the Adoptive Transfer of Regulatory T cells to Promote Bone Marrow Engraftment.PloS one · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4(+)CD25(+)Foxp3(+) Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7-14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII.
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