ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Induction of immune tolerance to a therapeutic protein by intrathymic gene delivery.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Central tolerance promoted by cell chimerism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cultured thymus tissue implantation promotes donor-specific tolerance to allogeneic heart transplants.JCI insight · 2020Article
- The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders.Journal of inherited metabolic disease · 2016Review
- Targeted approaches to induce immune tolerance for Pompe disease therapy.Molecular therapy. Methods & clinical development · 2016Review
- Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Development of Gene Transfer for Induction of Antigen-specific Tolerance.Molecular therapy. Methods & clinical development · 2014Article
- Administration of anti-CD3 antibodies modulates the immune response to an infusion of α-glucosidase in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector.Frontiers in microbiology · 2011Article
- Immunomodulatory strategies prevent the development of autoimmune emphysema.Respiratory research · 2010Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of recombinant enzyme therapy for genetic diseases is limited in some patients by the generation of a humoral immune response to the therapeutic protein. Inducing immune tolerance to the protein prior to treatment has the potential to increase therapeutic efficacy. Using an AAV8 vector encoding human acid α-glucosidase (hGAA), we have evaluated direct intrathymic injection for inducing tolerance. We have also compared the final tolerogenic states achieved by intrathymic and intravenous injection. Intrathymic vector delivery induced tolerance equivalent to that generated by intravenous delivery, but at a 25-fold lower dose, the thymic hGAA expression level was 10,000-fold lower than the liver expression necessary for systemic tolerance induction. Splenic regulatory T cells (Tregs) were apparent after delivery by both routes, but with different phenotypes. Intrathymic delivery resulted in Tregs with higher FoxP3, TGFβ, and IL-10 mRNA levels. These differences may account for the differences noted in splenic T cells, where only intravenous delivery appeared to inhibit their activation. Our results imply that different mechanisms may be operating to generate immune tolerance by intrathymic and intravenous delivery of an AAV vector, and suggest that the intrathymic route may hold promise for decreasing the humoral immune response to therapeutic proteins in genetic disease indications.
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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.