Abstract |
Preclinical safety and toxicity studies of intrapleural administration of recombinant adenovirus carrying the herpes simplex thymidine kinase gene (H5.010RSVtk) were performed. Previously reported experimental evidence has demonstrated the efficacy of this approach in animal models of a localized thoracic cancer, malignant mesothelioma. H5.010RSVtk was delivered at high dose (10(12) pfu) into the pleural cavity of three non-human primates followed by systemic administration of ganciclovir. No clinical toxicity was noted. Although an inflammatory reaction observable by microscopy was noted in the serosal spaces of the chest cavity, these changes were reversible and were not associated with radiographic sequelae. Extrathoracic viral dissemination was minimal and detectable only by sensitive polymerase chain reaction techniques. This low level of viral dissemination was not associated with detectable clinical, biochemical, or pathologic abnormalities.
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Authors | J C Kucharczuk, S Raper, A A Elshami, K M Amin, D H Sterman, E B Wheeldon, J M Wilson, L A Litzky, L R Kaiser, S M Albelda |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 7
Issue 18
Pg. 2225-33
(Dec 01 1996)
ISSN: 1043-0342 [Print] United States |
PMID | 8953313
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Viral
- Antimetabolites
- DNA, Recombinant
- DNA, Viral
- Thymidine Kinase
- Ganciclovir
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Topics |
- Adenoviridae
(genetics, immunology)
- Animals
- Antibodies, Viral
(blood)
- Antimetabolites
(administration & dosage)
- DNA, Recombinant
(adverse effects, analysis)
- DNA, Viral
(adverse effects, analysis)
- Drug Administration Routes
- Female
- Ganciclovir
(administration & dosage)
- Gene Transfer Techniques
(adverse effects)
- Genetic Vectors
(administration & dosage, adverse effects)
- Liver
(pathology)
- Lung
(pathology)
- Male
- Neutralization Tests
- Organ Specificity
- Papio
- Pleura
(pathology)
- Safety
- Simplexvirus
(enzymology, genetics)
- Thymidine Kinase
(genetics)
- Transgenes
- Virus Shedding
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