ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Adenovirus-Antibody Complexes Contributed to Lethal Systemic Inflammation in a Gene Therapy Trial.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- Vectored Immunoprophylaxis for Mucosal Immunity: Advances and Challenges Associated with Recombinant Secretory IgA Expression.Vaccines · 2026Review
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Immune shielding of viral vectors via capsid engineering with genetically encoded zwitterionic peptides.Molecular therapy. Advances · 2026Article
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- Current regulatory requirements for assessment of immunogenicity for gene therapy medicinal products.Cell reports. Medicine · 2025Review
- Peeling back the layers of immunogenicity in Cas9-based genomic medicine.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Novel Lung Cell-Penetrating Peptide Targets Alveolar Epithelial Type II Cells, Basal Cells, and Ionocytes.Pharmaceutics · 2025Article
- Four decades of adenovirus gene transfer vectors: History and current use.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene therapy then and now: A look back at changes in the field over the past 25 years.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Immune remodulation in pediatric inherited metabolic liver diseases.World journal of hepatology · 2024Review
- Exploration of Gene Therapy for Alport Syndrome.Biomedicines · 2024Review
- High-dose systemic adeno-associated virus vector administration causes liver and sinusoidal endothelial cell injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Building CRISPR Gene Therapies for the Central Nervous System: A Review.JAMA neurology · 2024Review
- Gene Therapy for Genetic Syndromes: Understanding the Current State to Guide Future Care.Biotech (Basel (Switzerland)) · 2024Review
- Viral Vector-Based Gene Therapy.International journal of molecular sciences · 2023Review
- Nanoparticles and cytokine response.Frontiers in bioengineering and biotechnology · 2023Review
- Exosome-based drug delivery systems for the treatment of diabetes and its complications: current opinion.Extracellular vesicles and circulating nucleic acids · 2023Review
- Food and Drug Administration Guidance on Design of Clinical Trials for Gene Therapy Products with Potential for Genome Integration or Genome Editing and Associated Long-Term Follow-Up of Research Subjects.Applied biosafety : journal of the American Biological Safety Association · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Intra-arterial administration of an adenovirus serotype 5 (Ad5) vector in a gene therapy trial caused lethal, systemic inflammation in subject 019 with ornithine transcarbamylase deficiency. This unanticipated inflammatory response was absent in another subject receiving the same vector dose and in 16 subjects receiving lower vector doses. We hypothesized that an immune memory to a previous natural adenovirus infection enhanced the immune response to high-dose systemic Ad5 vector, causing the exaggerated immune response in subject 019. To investigate this, we found that rabbit polyclonal sera to Ad5 and pooled human immunoglobulin (Ig) inhibited Ad5 vector transduction of non-immune cells in vitro, but enhanced transduction and activation of human dendritic cells (DCs). Sera from approximately 7% of normal human subjects and 50% of patients treated topically with Ad5 vectors enhanced Ad5 transduction and activation of DCs, apparently from formation of Ig-Ad5 immune complexes and binding to DCs through FcγR. Subject 019's blood substantially increased Ad5-vector activation of human DC primary cultures at levels exceeding those from normal subjects. Although this study is based on one event in a single subject, the results implicate a pre-existing humoral immune response to Ad5 in the lethal systemic inflammatory response that occurred in subject 019.
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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.