Trial reportProceedings of the National Academy of Sciences of the United States of America2017
Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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.
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
51 citing papers in PubMed, 82 citations in OpenAlex.
- First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study.Gene therapy · 2026Trial
- Transient prophylactic immunosuppression with abatacept or dasatinib prevents immune responses in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The co-delivery of Programmed Death 1 ligands enhances and prolongs rAAV-mediated gene expression in pre-immunized mice.Gene therapy · 2026Article
- Combining Anti-Inflammatory Drugs and Cell-Specific Expression-Suppression Reduces the Adjuvant Activity of mRNA-LNPs.Molecular pharmaceutics · 2026Article
- Current regulatory requirements for assessment of immunogenicity for gene therapy medicinal products.Cell reports. Medicine · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Review
- Viral vectors in neurodegenerative diseases: immune responses and therapeutic applications.Frontiers in neurology · 2025Review
- Gene therapy of Dent disease type 1 in newborn ClC-5 null mice for sustained transgene expression and gene therapy effects.Gene therapy · 2024Article
- Redundancy in Innate Immune Pathways That Promote CD8Viruses · 2024Article
- Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier.Fluids and barriers of the CNS · 2024Article
- Role of FoxP3Human gene therapy · 2024Review
- Recent advances in nanoparticulate RNA delivery systems.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques.Gene therapy · 2024Article
- TLR9-independent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Sustained and Efficient Delivery of Antivascular Endothelial Growth Factor by the Adeno-associated Virus for the Treatment of Corneal Neovascularization: An Outlook for Its Clinical Translation.Journal of ophthalmology · 2024Review
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Immune Responses to Muscle-Directed Adeno-Associated Viral Gene Transfer in Clinical Studies.Human gene therapy · 2023Review
- A lentiviral vector B cell gene therapy platform for the delivery of the anti-HIV-1 eCD4-Ig-knob-in-hole-reversed immunoadhesin.Molecular therapy. Methods & clinical development · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV)-mediated gene therapy is currently being pursued as a treatment for the monogenic disorder α-1-antitrypsin (AAT) deficiency. Results from phase I and II studies have shown relatively stable and dose-dependent increases in transgene-derived wild-type AAT after local intramuscular vector administration. In this report we describe the appearance of transgene-specific T-cell responses in two subjects that were part of the phase II trial. The patient with the more robust T-cell response, which was associated with a reduction in transgene expression, was characterized more thoroughly in this study. We learned that the AAT-specific T cells in this patient were cytolytic in phenotype, mapped to a peptide in the endogenous mutant AAT protein that contained a common polymorphism not incorporated into the transgene, and were restricted by a rare HLA class I C alleles present only in this patient. These human studies illustrate the genetic influence of the endogenous gene and HLA haplotype on the outcome of gene therapy.
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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.