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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-8-4
pubmed:abstractText
Vaccination with cytokine-transduced tumor cells represents a potentially important approach to the treatment of central nervous system tumors. We have recently demonstrated the therapeutic efficacy of tumor cell vaccines expressing the murine interleukin 4 (IL-4) and the herpes simplex virus-thymidine kinase in a rat brain tumor model in which nonirradiated vaccine cells can be eliminated by the subsequent administration of ganciclovir. In this report, we demonstrate the construction and characterization of a retroviral vector that encodes human IL-4, neomycin phosphotransferase, and herpes simplex virus-thymidine kinase genes for use in human clinical trials. An MFG-based retroviral vector was used to generate the recombinant retrovirus, TFG-hIL4-Neo-Tk, in which a long terminal repeat-driven polycistronic transcript encodes three cDNAs that are linked and coexpressed using two intervening internal ribosome entry site fragments from the encephalomyocarditis virus. The amphotropic retroviral vector TFG-hIL4-Neo-Tk was then used to infect human primary glioma cultures and skin-derived fibroblasts. After infection and G418 selection, cells produced 89-131 ng/10(6) cells/48 hours of human IL-4, which was determined to be biologically active. Transduced glioma cells were highly sensitive to the cytotoxic effect of ganciclovir. These data demonstrate the suitability of the TFG-hIL4-Neo-Tk vector for therapeutic studies of cytokine-transduced autologous tumor vaccination in patients with malignant gliomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
486-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Characterization and transduction of a retroviral vector encoding human interleukin-4 and herpes simplex virus-thymidine kinase for glioma tumor vaccine therapy.
pubmed:affiliation
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. okadah@msx.upmc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't