infusions of autologous lymphocytes polyclonally stimulated in culture to permit retroviral- 
mediated transduction with a vector containing the hADA gene as well as the selectable gene Neo^ 
(vector LASN). Selection for gene-expressing cells will not be performed during Part 1 in 
order to shorten the culture period to maximize polyclonality of the reinfused ADA gene- 
corrected cells. No change to current PEG-ADA or immunoglobulin replacement therapy would 
be instituted during either part of this protocol. Information derived from Part 1 will 
provide data about the therapeutic effects of the ADA reconstituted cells on patient immune 
function as well as possible toxicities associated with cellular immunotherapy, survival of the 
transduced cells in vivo, and continued expression of the introduced genes in vivo. 
Part 2 of the proposal will consist of infusions of transduced cells which have been selected for 
expression of the introduced genes. During part 2.A. of the protocol, the autologous T cells will 
be infused as soon as they reach a level of hADA expression during culture selection which is 
similar to the ADA concentration found in normal blood cells. In part 2.B., an escalating 
schedule of infusions of the selected ADA gene-transduced cells will be given to determine 
whether sufficient cells could be given to eventually replace the requirement for PEG-ADA 
treatment. Based on the average level of ADA expression in ADA deficient T cells transduced 
with the UVSN vector this calculated cell number is approximately 1x10®/Kg. This cell dosage 
is similar to the number of cells infused during TIL therapy for cancer. 
In our original protocol submission we included a Part 3 during which PEG-ADA treatment 
would be stopped. This portion of the protocol has been withdrawn from this version because 
its design is critically dependent upon data to be generated during Parts 1 and 2 of the protocol, 
data we cannot predict with sufficient accuracy in advance of the actual human studies. We will 
return to the committee with an amended protocol containing the data from parts 1 and 2 if we 
determine that part 3 is indicated for certain patients. 
2.0 Objectives 
A) To evaluate the possible therapeutic efficacy of the administration of autologous lymphocytes 
transduced with a normal hADA gene in an effort to reconstitute the function of the cellular 
and humoral immune systems in patients with ADA(-)SCID. 
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Recombinant DNA Research, Volume 14 
