Trial reportHuman gene therapy2014
Immune responses to intramuscular administration of alipogene tiparvovec (AAV1-LPL(S447X)) in a phase II clinical trial of lipoprotein lipase deficiency gene therapy.
Trial report in Human gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Incidence, timing, and clinical significance of adverse immune events after gene replacement therapy: A systematic review and meta-analysis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- 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
- Overcoming host immune responses to an AAV-delivered HIV-1 bNAb in rhesus macaques mediated by co-delivery of PD-L1.bioRxiv : the preprint server for biology · 2026Article
- Incomplete elimination of viral genomes is associated with chronic inflammation in nonhuman primate livers after AAV-mediated gene transfer.Gene therapy · 2025Article
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Current AAV-mediated gene therapy in sensorineural hearing loss.Fundamental research · 2025Review
- Imaging of adeno-associated viral capsids for purposes of gene editing using CEST NMR/MRI.Magnetic resonance in medicine · 2024Article
- Role of FoxP3Human gene therapy · 2024Review
- AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Understanding AAV vector immunogenicity: from particle to patient.Theranostics · 2024Review
- Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases.Biomedicines · 2023Review
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy.The AAPS journal · 2023Review
- Engineered AAV8 capsid acquires heparin and AVB sepharose binding capacity but has altered in vivo transduction efficiency.Gene therapy · 2023Article
- Review
- Rational design of AAVrh10-vectored ACE2 functional domain to broadly block the cell entry of SARS-CoV-2 variants.Antiviral research · 2022Article
- Durability of transgene expression after rAAV gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications.Biomedicines · 2022Review
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular immune responses to adeno-associated viral (AAV) vectors used for gene therapy have been linked to attenuated transgene expression and loss of efficacy. The impact of such cellular immune responses on the clinical efficacy of alipogene tiparvovec (Glybera; AAV1-LPL(S447X); uniQure), a gene therapy consisting of intramuscular administration of a recombinant AAV1 mediating muscle-directed expression of lipoprotein lipase (LPL), was investigated. Five subjects with LPL deficiency (LPLD) were administered intramuscularly with a dose of 1 × 10(12) gc/kg alipogene tiparvovec. All subjects were treated with immune suppression starting shortly before administration of alipogene tiparvovec and maintained until 12 weeks after administration. Systemic antibody and T cell responses against AAV1 and LPL(S447X), as well as local cellular immune responses in the injected muscle, were investigated in five LPLD subjects. Long-term transgene expression was demonstrated despite a transient systemic cellular response and a stable humoral immune response against the AAV1 capsid protein. Cellular infiltrates were found in four of the five subjects but were not associated with adverse clinical events or elevation of inflammation markers. Consistent herewith, CD8+ T cells in the infiltrates lacked cytotoxic potential. Furthermore, FoxP3+/CD4+ T cells were found in the infiltrates, suggesting that multiple mechanisms contribute to local tolerance. Systemic and local immune responses induced by intramuscular injection of alipogene tiparvovec did not appear to have an impact on safety and did not prevent LPL transgene expression. These findings support the use of alipogene tiparvovec in individuals with LPLD and indicate that muscle-directed AAV-based gene therapy remains a promising approach for the treatment of human diseases.
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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.