Adenovirus gene transfer causes inflammation in the brain

Byrnes, Andrew P.; Rusby, J.E.; Wood, Matthew; Charlton, H. M.

doi:10.1016/0306-4522(95)00068-t

Cited by 270 publications

(191 citation statements)

References 45 publications

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“…Thus, in vivo, expression of these wt Ad genes leads to a host inflammatory response which hinders the use of this vector for clinical purposes outside cancer therapy (Byrnes et al, 1995;Byrnes et al, 1996;Dewey et al, 1999;Lowenstein and Castro, 2003;Thomas et al, 2001a;Thomas et al, 2001b;Wood et al, 1996). Moreover, rAd infection induces well characterized innate and adaptive immune responses in the brain (Byrnes et al, 1995;Byrnes et al, 1996;Dewey et al, 1999;Lowenstein and Castro, 2003;Thomas et al, 2001a;Thomas et al, 2001b;Wood et al, 1996). Newer Ad vectors have been designed that retain only the inverted terminal repeats, i.e., with all viral genes removed; the so-called gutless vectors or high-capacity vectors (Hardy et al, 1997;Parks et al, 1996;Thomas et al, 2001b).…”

Section: Recombinant Adenovirus (Rad)mentioning

confidence: 99%

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Mandel

Bürger

Snyder

2008

Experimental Neurology

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Because Parkinson's disease is a progressive degenerative disorder that is mainly confined to the basal ganglia, gene transfer to deliver therapeutic molecules is an attractive treatment avenue. The present review focuses on direct in vivo gene transfer vectors that have been developed to a degree that they have been successfully used in animal model of Parkinson's disease. Accordingly, the properties of recombinant adenovirus, recombinant adeno-associated virus, herpes simplex virus, and lentivirus are described and contrasted. In order for viral vectors to be developed into clinical grade reagents, they must be manufactured and tested to precise regulatory standards. Indeed, clinical lots of viral vectors can be produced in compliance with current Good Manufacturing Practices (cGMPs) regulations using industry accepted manufacturing methodologies, manufacturing controls, and quality systems. The viral vector properties themselves combined with physiological product formulations facilitate long-term storage and direct in vivo administration.

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Section: Recombinant Adenovirus (Rad)mentioning

confidence: 99%

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Mandel

Bürger

Snyder

2008

Experimental Neurology

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“…25,30 Most likely, fiber and/or hexon proteins stimulate cytokine release, resulting in increased levels of TNF-␣, IL-1 and IL-6. 40 Recently, a critical role in acute inflammation has been suggested for adenovirus-induced IL-8 production.…”

Section: Activated Astrocytes (Gliosis) Around the Lesion Are Seen Bymentioning

confidence: 99%

“…30,43 After virus injection into the rat brain, however, polymorphonuclear cells are almost always absent. 25,29 The second phase of the immune response is often attributed to low level expression of viral proteins. 30 Recent experiments, however, have shown the importance of the immunogenicity of the (non-self) transgene- encoded protein rather than the viral proteins in eliciting this inflammatory reaction.…”

Section: Activated Astrocytes (Gliosis) Around the Lesion Are Seen Bymentioning

confidence: 99%

“…Local administration of replication defective adenovirus vectors to the brain (and visceral organs) induces an inflammatory reaction by eliciting a biphasic immune response. [25][26][27][28][29] The early, innate, phase of the immune response is characterized by infiltration of neutrophils and macrophages and is followed by a T celldependent adaptive immune response. The immune response is not only toxic but also contributes to the decline of transgene expression because of the elimination of infected or transduced cells by cytotoxic T cells.…”

Section: Introductionmentioning

confidence: 99%

“…The immune response is not only toxic but also contributes to the decline of transgene expression because of the elimination of infected or transduced cells by cytotoxic T cells. [25][26][27][28][29][30][31] Goodman et al 32 observed significant neurotoxicity of adenotk, potentiated by GCV, in baboons. Two animals in which the intracerebral injection of a high dose of adenotk was followed by treatment with GCV died from increased intracranial pressure.…”

Section: Introductionmentioning

confidence: 99%

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Intracerebral injection of adenovirus harboring the HSVtk gene combined with ganciclovir administration: toxicity study in nonhuman primates

et al. 1998

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A high dose (1-2.5 × 10 10 infectious units) of recombinant vated astrocytes (gliosis). Immunohistochemical analysis adenovirus harboring the herpes simplex thymidine kinase of the infiltrates revealed the presence of predominantly gene (IG.Ad.MLPI.TK) was injected into the white matter mononuclear cells. In the vicinity of the lesion perivascular of the right frontal lobe in two rhesus monkeys (M. mulatta).cuffs were seen containing T lymphocytes and clusters of Injection of the vector was followed by systemic ganciclovir B lymphocytes. From this preclinical study we conclude administration (10 mg/kg per day) for 14 days. During treatthat the toxicity of adenotk/GCV is acceptable and treatment no clinical symptoms were observed. Histopathoment of patients with malignant gliomas using this kind of logical analysis of the brain at day 18 showed a 5 mm nectherapy is feasible. However, careful dose finding in clinical rotic area at the site of the virus injection. This area was studies is recommended. invaded and surrounded by inflammatory cells and acti-

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Concept of autoimmunity following spinal cord injury: Possible roles for T lymphocytes in the traumatized central nervous system

1996

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Adenovirus gene transfer causes inflammation in the brain

Cited by 270 publications

References 45 publications

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Intracerebral injection of adenovirus harboring the HSVtk gene combined with ganciclovir administration: toxicity study in nonhuman primates

Concept of autoimmunity following spinal cord injury: Possible roles for T lymphocytes in the traumatized central nervous system

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