Recombinant DNA Advisory Committee - 2/10-11/92 
that while the patients are doing extremely well, they are not normal and are at risk of 
death if exposed to antigens for which they have no immune response. The only change to 
the original protocol involves adding the new stem cell therapy, and there will be no fewer 
peripheral T lymphocyte treatments. Hie researchers perform PCR analysis to 
differentiate the two vectors and observe results. If the patients develop granulocytes and 
monocytes that contain the new vector and the immune function studies are in the normal 
range, the next consideration will be to withdraw PEG- ADA and to later on possibly 
withdraw T lymphocyte treatment. 
Dr. Gellert asked why other patients who were currently only on PEG-ADA would not be 
chosen for this therapy. By choosing the patients who were already being treated with 
another therapy, the two therapies could be confounded. Dr. Culver stated that there are 
many patients waiting for stem cell therapy. However, these patients are not the best 
candidates to enter this protocol. It would be better to begin with patients who are 
already being treated and add the stem cells since the investigators would be able to 
differentiate which populations of cells are mediating long-term survival or immune 
recovery in the blood. Dr. Anderson reemphasized that there is a balance between what is 
best for the patient, what is scientifically best, and what is emotionally important for the 
families. It might complicate determining what procedure really benefits the patients if 
CD34(+) cells are inserted, even though they are marked differently. It is the 
investigators' view that if the patients benefit, such a result could be sorted out in later 
patients. 
Dr. Mclvor asked about the evidence for gene transfer into hematopoietic stem cells 
capable of differentiating into lymphocyte lineages. Dr. Nienhuis answered that data from 
the murine model showed that using the developed conditions, genes could be reliably 
introduced into cells; and those genes could be expressed with a variety of different 
vectors. Dr. Nienhuis acknowledged that the data in higher animal systems is less 
advanced, but indicates that full reconstitution is possible. One higher animal model 
demonstrates that when genes are introduced into CD34 enriched cells using retroviral 
vectors, there is a result in detection of the gene in multi-lineage cells as much as six 
months later. Data from Dr. Valerio indicates that ADA expression is detected as long as 
one year after the transplant. 
Dr. Mclvor questioned whether ADA assays had been performed on CD34 enriched cells 
transduced with GlNa.SvAd. Dr. Nienhuis answered that this cell population has not been 
assayed; however, neomycin resistance gene selections have been completed, and that the 
neomycin resistance gene is being expressed. ADA expression has been studied in T 
lymphocytes but not in CD34 enriched cells. Dr. Anderson stated that this is difficult 
because both patients now have ADA corrected cells. Consequently, there are no true 
ADA deficient cells, except the old TJF2 in which assays have been completed. TJF2 is 
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