Intracranial Administration of Adenovirus Expressing HSV-TK in Combination with Ganciclovir Produces a Dose-Dependent, Self-Limiting Inflammatory Response

Smith, Jason G.; Raper, Steven E.; Wheeldon, Eric B.; Hackney, David B.; Judy, Kevin; Wilson, James M.; Eck, Stephen L.

doi:10.1089/hum.1997.8.8-943

Cited by 60 publications

(34 citation statements)

References 27 publications

(15 reference statements)

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“…Similar histopathological results have been reported by Smith et al 35 who administered even higher doses of adenotk into rhesus monkey brains than we did. In contrast, one out of two baboons treated by Goodman et al 32 that received 1.5 × 10 9 plaque forming units (p.f.u.)…”

Section: Figure 2 He Staining Of the Brain At The Site Of Vector Admisupporting

confidence: 92%

“…However, a dose of 1 × 10 9 IU recombinant adenoviral particles produces focal malacia and mononuclear infiltrates spreading along the white matter tract. 39 Comparable dose-dependent changes were reported by Smith et al 35 in Wistar rats and in rhesus monkeys. Also, Goodman et al 32 observed severe clinical and neuropathological toxicity in high-dose monkeys only.…”

Section: Figure 2 He Staining Of the Brain At The Site Of Vector Admimentioning

confidence: 69%

“…In addition, those authors observed no important differences in the pathologic findings after intracerebral adenovirus administration in Wistar rats receiving dexamethasone compared with those that did not receive dexamethasone. 35 This may indicate the limited influence of the perioperative use of steroids. However, at this time, the contribution of the immune response in the elimination of established brain tumors using the HSVtk/GCV system is not known.…”

Section: Figure 2 He Staining Of the Brain At The Site Of Vector Admimentioning

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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Section: Figure 2 He Staining Of the Brain At The Site Of Vector Admisupporting

confidence: 92%

Section: Figure 2 He Staining Of the Brain At The Site Of Vector Admimentioning

confidence: 69%

Section: Figure 2 He Staining Of the Brain At The Site Of Vector Admimentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 1998

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“…Coagulative necrosis, edema, and perivascular lymphocytosis were observed with intensive treatment. Smith et al 23 also noted local toxicity of the same system in rat brains. In our previous study, necrosis, demyelination, and gliosis were recognized in 5 -FC / CD gene therapy for brain tumors.…”

Section: Discussionmentioning

confidence: 91%

Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes

et al. 2002

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“…The canine kidney cell line DK 12 was grown in Dubbelco's modi®ed Eagle's medium (Gibco BRL) supplemented with 10% FCS.…”

Section: Cell Cultures and Recombinant Adenoviral Vectormentioning

confidence: 99%

Adenovirus-mediated gene transfer in dog prostate: a preclinical study of a relevant model system for gene therapy of human prostatic cancer

Andrawiss¹,

Opolon²,

Benihoud³

et al. 1999

Prostate Cancer Prostatic Dis

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This present study evaluates the potential of adenovirus-mediated gene transfer (AMGT) to the prostate of normal laboratory beagles. Many morphological and histological similarities can be noted between dog and human prostate. Moreover, dogs can spontaneously develop prostate cancer with a clinical and biological outcome identical to that in man. Firstly we showed the capacity of human adenovirus to infect canine prostatic cells in vitro. Secondly, we injected transrectally in the dogs' prostates 2610 9 plaque forming units of a ®rst generation recombinant adenovirus vector harboring the reporter gene b-galactosidase (AdRSVbgal). Seven days after the adenoviral delivery, we observed expression of the transgene in both prostates, and exclusively in epithelial cells. Despite a cellular and a humoral immune response, the infusion appeared safe, since the dogs had no fever and presented no urinary symptoms. This study constitutes the ®rst evaluation of AMGT in dog prostate and provides a basis for gene therapy treatment of prostate carcinoma-bearing patients.

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Intracranial Administration of Adenovirus Expressing HSV-TK in Combination with Ganciclovir Produces a Dose-Dependent, Self-Limiting Inflammatory Response

Cited by 60 publications

References 27 publications

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

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

Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes

Adenovirus-mediated gene transfer in dog prostate: a preclinical study of a relevant model system for gene therapy of human prostatic cancer

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