Scientific Abstract 
Murine retroviral vectors can infect a wide variety of proliferating mammalian cell types (e.g. 
lymphocytes). Non-proliferating tissues (e.g. neurons) are not transduced by murine retroviral 
vectors. These findings suggest that this type of vector may be useful for the selective 
introduction of genes into growing tumors in the brain, since the tumor is essentially the only 
tissue that would integrate and express the vector genes. 
We investigated the possibility of in vivo transduction of growing brain tumors with the herpes 
simplex thymidine kinase (HS-tk) gene. Rats with a malignant brain tumor were given an 
intratumoral stereotaxic injection of murine fibroblasts that were producing a retroviral vector 
containing the herpes simplex thymidine kinase (HS-tk) gene or a control vector producer cell 
line containing the (3-galactosidase gene. The animals were rested 5 days to allow time for the 
HS-tk retroviral vectors that were produced in situ to transduce the neighboring proliferating 
glioma. The animals were then treated with the anti-herpes drug ganciclovir (GCV). Gliomas 
injected with the HS-tk producer cells regressed completely with GCV therapy while the tumors 
injected with p-galactosidase producers had large tumors. Staining for p-galactosidase positive 
cells in control animal brain revealed transduction of 40-80% of the tumor cells without evidence 
of transduction of the surrounding normal brain tissue. No significant toxicity was observed in 
toxicity studies in mice, rats and non-human primates. 
Based upon these findings, we have proposed a human clinical trial to determine if the direct 
injection of the GITkSvNa producer cell line into growing human brain tumors will regress with 
GCV therapy. The patient population consists of individuals with recurrent malignant tumors who 
survival of of these patients is limited to weeks to a few months. 
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Recombinant DNA Research, Volume 15 
