ArticleHuman gene therapy2017
Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone.
Article in Human gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 20 citations in OpenAlex.
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 2025Article
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques.Gene therapy · 2024Article
- Prophylactic Prednisolone Promotes AAV5 Hepatocyte Transduction Through the Novel Mechanism of AAV5 Coreceptor Platelet-Derived Growth Factor Receptor Alpha Upregulation and Innate Immune Suppression.Human gene therapy · 2024Article
- Immunosuppression reduces rAAV2.5T neutralizing antibodies that limit efficacy following repeat dosing to ferret lungs.Molecular therapy. Methods & clinical development · 2023Article
- Biochemical Correction of GM2 Ganglioside Accumulation in AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
- Single-Dose Intrathecal Dorsal Root Ganglia Toxicity of Onasemnogene Abeparvovec in Cynomolgus Monkeys.Human gene therapy · 2022Article
- Immunomodulation in Administration of rAAV: Preclinical and Clinical Adjuvant Pharmacotherapies.Frontiers in immunology · 2021Review
- Article
- rAAV8 and rAAV9-Mediated Long-Term Muscle Transduction with Tacrolimus (FK506) in Non-Human Primates.Molecular therapy. Methods & clinical development · 2020Article
- Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020Review
- Overcoming Immunological Challenges to Helper-Dependent Adenoviral Vector-Mediated Long-TermGenes · 2020Article
- rAAVrh74.MCK.Molecular therapy. Methods & clinical development · 2019Article
- Soluble Heparin Binding Epidermal Growth Factor-Like Growth Factor Is a Regulator ofMolecular and cellular biology · 2019Article
- Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with No Detectable Immunity.Human gene therapy · 2019Article
- Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.Journal of inherited metabolic disease · 2018Article
- An Isolated Limb Infusion Method Allows for Broad Distribution of rAAVrh74.MCK.Molecular therapy. Methods & clinical development · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post AAV delivery compared with AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment. The majority of CD8+ T cells in AAV-treated muscles expressed activated caspase 3 and programmed cell death protein 1 (PD1), suggesting ongoing programmed cell death. AAV-transduced skeletal muscles also had elevated expression of programmed death ligand 2 (PDL2) on skeletal myofibers, and this increase in expression extended to muscles where transgene was not overexpressed. These data demonstrate that prednisone can reduce the extent of intramuscular T-cell infiltrates in AAV-treated muscles, which may aid in achieving long-term transgene expression, as may the induction of PDL2 expression on skeletal myofibers to promote PD1-mediated programmed T-cell death.
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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.