CNS 18 - 8 
retroviral vector LNL6 (constructed by A. Dusty Miller; 
supernatant produced by Genetic Therapy, Inc). The GITKSVNa 
vector to be used in the current protocol is modelled on the LNL6, 
having the same general structure and safety modification. None 
of the patients have demonstrated any untoward effects since 
receiving the genetically-altered cells (17). 
Human Gene Therapy for Adenosine Deaminase Deficiency (ADD) 
Since September, 1990, two children have been enrolled on a 
protocol treating adenosine deaminase associated (ADA) immune 
deficiency. Fifteen intravenous infusions of autologous T-cells 
transduced by the LNSN vector have been administered to these 
patients and significant improvement of their severe 
immunodeficiency has occurred. The LASN vector (constructed 
by A. Dusty Miller; supernatant produced by Genetic Therapy, 
Inc.) is based on the LNL6 vector and therefore has the same 
general structure and safety modifications as the GITKSVNa 
vector proposed for use in the current protocol. Neither child has 
demonstrated any evidence of adverse effects due to the genetically 
altered cells. 
Other Human Gene Therapy Experiments 
A number of other gene-marking experiments (such as those being 
done currently at St. Jude in patients with acute non-lymphoblastic 
leukemia and neuroblastoma) as well as therapeutic experiments 
have been underway for over 18 months. More than 80 patients 
have been treated. No untoward side effects related to retroviral 
mediated gene transfer have been observed in any individual. 
The above experiences with retroviral-mediated gene transfer suggests that 
therapeutic approaches using this technology are reasonably safe, and may possess 
efficacy. The experiences outlined above and the poor prognosis of recurrent 
malignant pediatric CNS tumors support initiating a phase I trial to evaluate the 
safety of retroviral vector therapy in pediatric patients with recurrent brain 
tumors. 
2.4 Preclinical Retroviral HS-tk Gene Therapy Studies 
Investigators of NINDS, NIH have performed a number of pre-clinical studies 
which demonstrate that retroviral transduction of xenogeneic genes can be done 
efficiently. Safety and antitumor efficacy have been shown in rodents and non- 
human primates. Due to the large amount of such information, all of which has 
been previously reviewed by the RAC, it is summarized in Protocol Appendix I. 
Recombinant DNA Research, Volume 18 
[311] 
