Non-Technical Abstract 
PROJECT TITLE: Gene Therapy for the Treatment of Malignant Brain Tumors 
with In Vivo Tumor Transduction with the Herpes Thymidine 
Kinase Gene/Ganciclovir System. 
PRINCIPAL INVESTIGATORS: Corey Raffel, M.D., Ph.D. and Kenneth W. 
Culver, M.D. 
NON-TECHNICAL ABSTRACT 
The possibility of transferring a "sensitivity" gene into a growing 
brain tumor has been investigated. The purpose is to make the tumor 
sensitive to a type of chemotherapy that is relatively non-toxic to the 
rest of the body. The gene selected is the Herpes Simplex-thymidine 
kinase (HS-tk) gene. Herpes Simplex is a virus that can be killed by 
a drug called ganciclovir (GCV) . By transferring the HS-tk gene into 
the tumor, using a disabled mouse virus called a "vector", the tumor 
will become like a herpes virus and the tumor can be killed with GCV. 
Experiments in rats have shown that the direct injection of mouse 
cells producing a HS-tk vector into a growing brain tumor can result in 
complete destruction of the tumor with GCV therapy. We found no 
evidence of spread of the virus to the normal brain tissue or to other 
parts of the body. Based upon these findings, an initial trial is 
underway at the National Institutes of Health (NIH) . To date eight 
people have been treated without evidence of toxicity. A second trial 
in adults has been approved. We now propose a human clinical trial for 
pediatric patients who are currently ineligible for treatment in the 
adult trials. In this study children with recurrent malignant brain 
tumors will be treated by injection of HS-tk vector-producer cells (VPC) 
into their tumors in an attempt to induce regression of the tumor with 
GCV therapy. The patient population consists of children who have 
failed standard therapy and have recurrent primary brain tumors with an 
expected survival of weeks to a few months. 
Recombinant DNA Research, Volume 18 
[51] 
