July 30, 1990, Human Gene Therapy Subcoomittee 
1. It was now clear that this was a series of experiments involving one patient, 
done over a period of months. 
2. It was clear there was a marked improvement in the child with PEG- ADA 
treatment. This leads to asking the question to what degree are the 
positive results in the mouse due to positive results in the patient and 
whether, if the patient had not responded as well, the mouse would have 
responded the same. 
3. It was observed that T cells from the patient's peripheral blood were 
capable of division in response to a specific antigen as a consequence of 
ADA therapy and that the child was able to make antibodies to tetanus 
toxoid. This means the T and B cells were capable of functioning in an 
antigen-specific manner prior to putting the ADA gene in. 
4. Figure 2 was clarified. It is now clear that the proliferative responses of 
the peripheral blood T lymphocytes of the patients make it likely that this 
is a polyclonal response and that the patient's peripheral blood cells are 
capable of responding to antigens. 
5. The issue of the diagnostic bands and staining was made clearer. However 
the question remains as to whether the insertion of the ADA gene is not a 
prerequisite for the antigen-specific immune function because the 
peripheral blood T cells in this patient are capable of antigen-specific 
function in terms of blastogenesis and can cooperate with B cells to make 
specific antibody before the gene is inserted. It appears that the insertion 
of the gene permits the cells to survive in vivo in the mouse and shows that 
this result is like the NIH investigators' data indicating that ADA- 
containing T cells survive longer in culture than T cell lines that do not 
contain the vector. 
Dr. Parkman said his interpretation of the data was that the insertion of the human 
ADA gene into ADA-deficient T cells permits the T cells to survive longer in vivo than 
mock-infected cells. The investigators' hypothesis is that insertion of this gene into the 
peripheral T cells of patients who have a lesser degree of immune function would allow 
the prolonged survival of the cells, some of which would be antigen-specific and 
therefore would have a damming effect, or recruitment effect, on antigen-specific T cells. 
Further, the main point of the data is that the insertion gene has nothing to do with 
antigen-specific immune function, but rather has primarily to do with persistence of these 
cells in vivo in this model system. 
Dr. Mulligan asked if there was a need to culture these cells quickly and whether the 
assay system was functional. Dr. Bordignon said that if the cells are cultured for a long 
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