Gene Therapy for the Treatment of Brain Tumors Using Intra-Tumoral 
Transduction with the Thymidine Kinase Gene and Intravenous 
Ganciclovir. 
This protocol presents a new therapeutic approach to the treatment of patients with 
otherwise incurable malignant brain tumors. The strategy involves the preferential 
introduction of a drug-susceptibility gene into proliferating tumor tissue. This is accomplished 
by stereotaxic infiltration of the brain tumor with murine cells engineered to produce a 
retroviral vector which carries the gene for herpes simplex thymidine kinase. The injected 
vector-producer cells will continuously release HS-tk-carrying virus in the vicinity of the tumor 
over a period of days. Retroviral vectors will only transfer genes into proliferating cells and, in 
the brains of these patients, the only mitotically active cells will be the tumors. 
The herpes TK gene confirs sensitivity upon the cells expressing the gene to the 
antiviral drug ganciclovir (GCV). GCV is nontoxic to normal tissues, but will kill cells (eg. 
tumors) expressing this herpes virus enzyme. Our data also suggest that bystander tumor 
cells, not expressing HS-tk, may also be killed as a consequence of this process, amplifying 
the antitumor effects of treatment (by a process not completely understood). 
Pr.fi.Qi ?: 
Malignant brain tumors are responsible for significant morbidity and mortality 
in both pediatric and adult populations. These common tumors present an enormous 
therapeutic challenge due to their poor outcome despite radical surgery, high dose 
radiotherapy and chemotherapy. Survival of patients from the time of diagnosis is 
measured in months and recurrence after treatment is associated with a life expectancy 
of weeks. 
In an attempt to improve this grim prognosis of patients with malignant brain 
tumors (both primary tumors and secondary metastasis from systemic cancer such as 
melanoma, lung and breast cancer), we have developed a novel approach to the 
therapy of brain tumors. This approach makes use of recombinant DNA technology to 
transfer a sensitivity gene into a brain tumor. This is acheived by direct injection of the 
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Recombinant DNA Research, Volume 15 
