Pre-Clinical Summary 
The pre-clinical findings noted above suggest that the direct inoculation of 
a growing brain tumor with a HS-tk retroviral vector-producing cell line can mediate 
complete tumor rejection without the need for surgical excision, irradiation and/or 
traditional non-specific chemotherapy. In essence, this is an in vivo gene transfer 
methodology that selectively alters the sensitivity of a tumor cell to chemotherapy. 
Therefore, treatment with GCV does not result in widespread damage to the host 
immune system like many forms of chemotherapy. 
Our animal studies have demonstrated no significant toxicity to the normal 
brain tissue or any of the proliferating non-CNS tissues evaluated suggesting that the 
implantation of vector producer cells in a brain tumor is not associated with non- 
specific systemic toxicity. Having no suitable brain tumor model in non-human 
primates, we propose a human clinical research protocol for the treatment of human 
brain tumors by the direct injection of GITKSVNa vector-producing cells into primary 
and metastatic brain tumors. 
III. Selection of Patients 
All adults, greater than 18 years of age, with malignant brain tumors (primary 
and metastatic) who failed all standard therapy for their disease will be eligible to enter 
the study. Patients will be divided into two groups based on the surgical accessibility of 
their lesions as estimated from the pre-treatment radiological evaluation. These 
decisions will be made by the PI in accordance with the standards of care of 
neurosurgical practice. 
Group 1. Patients in whom the lesion(s) is (are) surgically accessible with acceptable 
operative risk. 
This group will provide necessary information regarding the efficiency of in-vivo 
transduction in the brain tumor after 5 days. In this group of patients the evaluation of 
the biological effect of tumor regression is limited and prolonged by the operative 
attempt at maximal tumor resection. 
Group 2. Patients in whom the lesion(s) are surgically inaccessible or the operative 
risk is unacceptably high. 
This group of patients will provide information regarding the effect of this treatment on 
[804] 
Recombinant DNA Research, Volume 15 
