ArticleGene therapy2000
Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity.
Article in Gene therapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 73 citations in OpenAlex.
- Advances in oncolytic virus delivery strategies and challenges in clinical translation.Materials today. Bio · 2026Review
- Protective role of aconitate decarboxylase 1 in neuroinflammation-induced dysfunctions of the paraventricular thalamus and sleepiness.Communications biology · 2024Article
- Challenges and strategies toward oncolytic virotherapy for leptomeningeal metastasis.Journal of translational medicine · 2024Review
- Oncolytic HSV1 targets different growth phases of breast cancer leptomeningeal metastases.Cancer gene therapy · 2023Article
- Application of single and cooperative different delivery systems for the treatment of intervertebral disc degeneration.Frontiers in bioengineering and biotechnology · 2022Review
- Identification and characterization of human nucleus pulposus cell specific serotypes of adeno-associated virus for gene therapeutic approaches of intervertebral disc disorders.BMC musculoskeletal disorders · 2015Article
- Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy.Gene therapy · 2013Article
- Rapamycin enhances adenovirus-mediated cancer imaging and therapy in pre-immunized murine hosts.PloS one · 2013Article
- Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm.International journal of nanomedicine · 2013Article
- Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model.The spine journal : official journal of the North American Spine Society · 2012Article
- Truncating the i-leader open reading frame enhances release of human adenovirus type 5 in glioma cells.Virology journal · 2011Article
- Antisense-mediated RNA targeting: versatile and expedient genetic manipulation in the brain.Frontiers in molecular neuroscience · 2011Article
- The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier.Journal of drug delivery · 2011Article
- Immunological priming potentiates non-viral anti-inflammatory gene therapy treatment of neuropathic pain.Gene therapy · 2009Article
- DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for therapeutic rescue of sensory neuronopathies in mice.The Journal of clinical investigation · 2009Article
- Long-term control of neuropathic pain in a non-viral gene therapy paradigm.Gene therapy · 2009Review
- AAV for pain: steps towards clinical translation.Gene therapy · 2009Review
- IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis.Gene therapy · 2008Article
- Absence of an intrathecal immune reaction to a helper-dependent adenoviral vector delivered into the cerebrospinal fluid of non-human primates.Gene therapy · 2008Article
- Blood-brain barrier transport of non-viral gene and RNAi therapeutics.Pharmaceutical research · 2007Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High doses of adenotk were injected into the cerebrospinal fluid of rats and nonhuman primates (Macaca mulatta). Vector administration was followed by ganciclovir administration for 14 days. Despite the absence of clinical symptoms, analysis of the cerebrospinal fluid (CSF) and histopathological examination of the central nervous system (CNS) of the monkeys (3 weeks after vector injection) were consistent with a viral meningitis. Immunohistochemical analysis of the inflammatory infiltrates in the monkeys revealed the presence of T and B lymphocytes, indicating a combined cellular and humoral immune response to the vector. This latter was supported by the finding of intrathecal anti-adenovirus antibody synthesis. Rats receiving high intrathecal adenotk doses showed a transient and dose-dependent clinical toxicity consisting of lethargy, hyperemic eyes and weight loss. Histopathological examination of the meninges showed a shift from polymorphonuclear infiltrates during the first post-injection days to clusters of mononuclear cells after 7 days. Acute toxicity is probably related to the early, innate immune response to the vector. In a separate experiment, high levels of IL-8 and IL-6, were measured during the first 2-3 post-injection days in the CSF of two monkeys which received intrathecal adenoLacZ. Therefore, these cytokines seem to play an important role in initiating the nonspecific immune response. In one monkey which received adenotk, recombinant adenovirus was cultured from serum samples obtained at the 7th post-injection day. At this time-point, no vector could be isolated from CSF samples. Based on these preclinical data, we recommend careful dose finding for clinical studies that aim to treat patients with leptomeningeal metastases.
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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.