ArticleProceedings of the National Academy of Sciences of the United States of America2006
Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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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.
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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
62 citing papers in PubMed, 104 citations in OpenAlex.
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Innate Immune Sensing of Adeno-Associated Virus Vectors.Human gene therapy · 2024Review
- Suppression of pullulanase-induced cytotoxic T cell response with a dual promoter in GSD IIIa mice.JCI insight · 2022Article
- Single-dose AAV vector gene immunotherapy to treat food allergy.Molecular therapy. Methods & clinical development · 2022Article
- Gene therapy - are we ready now?Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- Autologous bone marrow-derived MSCs engineered to express oFVIII-FLAG engraft in adult sheep and produce an effective increase in plasma FVIII levels.Frontiers in immunology · 2022Article
- Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells.Molecular therapy. Methods & clinical development · 2021Article
- Homodimeric Minimal Factor H:Frontiers in immunology · 2021Article
- Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model.Molecular therapy. Methods & clinical development · 2020Article
- Structure of the AAVhu.37 capsid by cryoelectron microscopy.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies for Hemophilia A Patients.International journal of molecular and cellular medicine · 2020Review
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- Role of Regulatory T Cell and Effector T Cell Exhaustion in Liver-Mediated Transgene Tolerance in Muscle.Molecular therapy. Methods & clinical development · 2019Article
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Liver induced transgene tolerance with AAV vectors.Cellular immunology · 2019Review
- Update on clinical gene therapy for hemophilia.Blood · 2019Review
- Tolerance induction in hemophilia: innovation and accomplishments.Current opinion in hematology · 2018Review
- Optimized Adeno-Associated Viral-Mediated Human Factor VIII Gene Therapy in Cynomolgus Macaques.Human gene therapy · 2018Article
- Emerging Issues in AAV-MediatedMolecular therapy. Methods & clinical development · 2018Review
- Gene Therapy With Regulatory T Cells: A Beneficial Alliance.Frontiers in immunology · 2018Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Treatment of genetic disease such as the bleeding disorder hemophilia B [deficiency in blood coagulation factor IX (F.IX)] by gene replacement therapy is hampered by the risk of immune responses to the therapeutic gene product and to the gene transfer vector. Immune competent mice of two different strains were tolerized to human F.IX by hepatic gene transfer mediated by adenoassociated viral vector. These animals were subsequently challenged by systemic administration of an E1/E3-deleted adenoviral vector, which is known to induce a cytotoxic T lymphocyte response to the transgene product. Immune tolerance prevented cytotoxic T lymphocyte activation to F.IX and CD8(+) cellular infiltrates in the liver. Moreover, a sustained and substantial increase in hepatic F.IX expression from the adenoviral vector was achieved despite in vitro T cell responses to adenoviral antigens. Cytolytic responses to therapeutic and to viral vector-derived antigens had been prevented in vivo by activation of regulatory CD4(+) T cells, which mediated suppression of inflammatory lymphocyte responses to the liver. This result suggests that augmentation of regulatory T cell activation should provide new means to avoid destructive immune responses in gene transfer.
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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.