brain, where the tumor is the predominant mitotic cell type, maximizing specific 
transduction of tumor with minimal, or absent, transduction of normal brain. These 
Moloney murine leukemia virus-based (MoMLV) vectors have been designed to 
minimize the possibility of recombinantion resulting in regeneration of a replication- 
competent virus (12, 13). 
3. Experience with Retroviral-mediated Gene Transfer Into Humans 
(Appendix F). 
N2/TIL Markina Study 
In 1989, the first gene transfer experiment in humans was conducted at the 
NIH. This study involved the treatment of 10 patients with autologous T-cells (TIL) that 
have been transduced with a retroviral-vector. The vector used in this experiment was 
LNL6 (constructed by A. Dusty Miller; supernate produced by Genetic Therapy Inc.) 
which has the same general structure and safety modifications as the GITKSVNa 
vector we propose to use. None of these patients have demonstrated any untoward 
effects secondary to receiving the genetically-altered cells (14). 
Human Gene Therapy for Adenosine Deaminase Deficiency 
2 children have been enrolled in this protocol since it opened in September, 
1990. 15 intravenous infusions of genetically altered autologous T-cells have been 
administered. These children had significant immunodeficiency before receiving these 
genetically-altered cells, but they have substantially improved after infusions of the 
LASN-modified cells. They have been treated with the LASN vector (constructed by A. 
Dusty Miller; supernate produced by Genetic Therapy Inc.) which, like LNL6, has the 
same general structure and safety modifications as the GITKSVNa vector that we will 
use. Neither child has demonstrated any evidence of adverse effect due to the 
genetically altered cells. 
Other Human Gene Therapy Experiments 
A number of other gene-marking experiments ( e.g. transduction of marrow 
cells in patients undergoing bone marrow transplantation) and therapy experiments 
(e.g. insertion of cytokine genes into autologous tumor in an effort to vaccinate a 
patients) are beginning. No untoward side effects related to retroviral mediated gene 
transfer have been observed in any patient. 
Recombinant DNA Research, Volume 15 
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