ArticleNeuron glia biology2006
Immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between T cells and virus-infected brain cells.
Article in Neuron glia biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Evolutionary basis of a new gene- and immune-therapeutic approach for the treatment of malignant brain tumors: from mice to clinical trials for glioma patients.Clinical immunology (Orlando, Fla.) · 2018Review
- The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors.Advances in pharmacology (San Diego, Calif.) · 2016Review
- Gene Therapy for the Treatment of Neurological Disorders: Central Nervous System Neoplasms.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Adenoviral vector-mediated gene therapy for gliomas: coming of age.Expert opinion on biological therapy · 2014Review
- Safety profile of gutless adenovirus vectors delivered into the normal brain parenchyma: implications for a glioma phase 1 clinical trial.Human gene therapy methods · 2012Article
- Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFNγ, perforin, and TNFα, and due to the elimination of transduced cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Influence of phospholipid composition on cationic emulsions/DNA complexes: physicochemical properties, cytotoxicity, and transfection on Hep G2 cells.International journal of nanomedicine · 2011Article
- The degenerating substantia nigra as a susceptible region for gene transfer-mediated inflammation.Parkinson's disease · 2011Article
- Exogenous fms-like tyrosine kinase 3 ligand overrides brain immune privilege and facilitates recognition of a neo-antigen without causing autoimmune neuropathology.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Gene transfer into rat brain using adenoviral vectors.Current protocols in neuroscience · 2010Article
- Evading the immune response upon in vivo gene therapy with viral vectors.Current opinion in molecular therapeutics · 2009Review
- Article
- Flt3L in combination with HSV1-TK-mediated gene therapy reverses brain tumor-induced behavioral deficits.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- In vivo polarization of IFN-gamma at Kupfer and non-Kupfer immunological synapses during the clearance of virally infected brain cells.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- One-year expression from high-capacity adenoviral vectors in the brains of animals with pre-existing anti-adenoviral immunity: clinical implications.Molecular therapy : the journal of the American Society of Gene Therapy · 2007Article
- Immune responses to adenovirus and adeno-associated vectors used for gene therapy of brain diseases: the role of immunological synapses in understanding the cell biology of neuroimmune interactions.Current gene therapy · 2007Review
- Immunology of neurological gene therapy: how T cells modulate viral vector-mediated therapeutic transgene expression through immunological synapses.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2007Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
First-generation adenovirus can be engineered with powerful promoters to drive expression of therapeutic transgenes. Numerous clinical trials for glioblastoma multiforme using first generation adenoviral vectors have either been performed or are ongoing, including an ongoing, Phase III, multicenter trial in Europe and Israel (Ark Therapeutics, Inc.). Although in the absence of anti-adenovirus immune responses expression in the brain lasts 6-18 months, systemic infection with adenovirus induces immune responses that inhibit dramatically therapeutic transgene expression from first generation adenoviral vectors, thus, potentially compromising therapeutic efficacy. Here, we show evidence of an immunization threshold for the dose that generates an immune response strong enough to eliminate transgene expression from the CNS. For the systemic immunization to eliminate transgene expression from the brain, > or = 1 x 10(7) infectious units (iu) of adenovirus need to be used as immunogen. Furthermore, this immune response eliminates >90% of transgene expression from 1 x 10(7)-1 x 10(3) iu of vector injected into the striatum 60 days earlier. Importantly, elimination of transgene expression is independent of the nature of the promoter that drives transgene expression and is accompanied by brain infiltration of CD8(+) T cells and macrophages. In conclusion, once the threshold for systemic immunization (i.e. 1 x 10(7) iu) is crossed, the immune response eliminates transgene expression by >90% even from brains that receive as little as 1000 iu of adenoviral vectors, independently of the type of promoter that drives expression.
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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.