Scientific Abstract 
Severe combined immunodeficiency (SCID) due to 
deficiency of the purine metabolic enzyme adenosine deaminase 
(ADA) is a fatal childhood immunodeficiency disease. Immune 
reconstitution by transplantation with HLA-identical bone marrow 
is the treatment of choice. For patients not candidates for bone 
marrow transplantation, we propose to attempt immune 
reconstitution by using infusions of autologous T lymphocytes 
expanded in tissue culture and genetically corrected by insertion 
of a normal ADA gene using retroviral-mediated gene transfer. 
The vector is LASN, in which the human ADA gene is promoted by 
the LTR while the NeoR gene is driven by the SV40 early gene 
promoter. The packaging line is PAS 17. 
The protocol is designed to have two parts. In Part 1, 
autologous gene-corrected T lymphocytes would be infused 
repeatedly in low numbers in order to build an immune repertoir 
of T cells and also to obtain information as to how long gene- 
corrected T cells survive in vivo. In Part 2A, the gene- 
corrected T cells would be selected in G418 and/or 
2 'deoxyadenosine and reinfused into the patient at monthly 
intervals for approximately six months. The goals would be 
essentially the same as in Part 1. In Part 2B, the number of 
gene-corrected T cells would be escalated in half-log increments 
to the predicted therapeutic level (probably around 1 x loV^g) . 
1-3 X lo’/kg gene-corrected cells would be infused several times 
and the patient would be monitored in order to determine if 
significant clinical improvement has occurred. 
Recombinant DNA Research, Volume 14 
[253] 
