Human Gene Therapy Subcommittee - 7/30/90 
he noted there was some confusion as to whether infusions would 
continue indefinitely or for a period of two years. He presented 
a written critique including the notation of typographical errors 
he had found in the document. He said he had no suggestions for 
revisions to the children's assent form. Both the assent form 
and the revised consent form were deemed to be splendid 
documents . 
Dr. Mclvor said he also had some concerns with the preclinical 
data presented from the Milan experiments. He said one of his 
main concerns was the overall efficiency of the gene transfer 
process being used. Only two of four animals showed human DNA 
sequences in spleen. Further, he said Figure 2 , as provided, was 
uninterpretable as to levels of ADA activity. However, Figure 5 
convinced him there was no problems with ADA expression. Further 
concerns in the experiments were: 
1. Control levels of CD4'^ human T cells in the mice; 
2. Levels of human immunoglobulins obtained when normal 
peripheral blood lymphocytes are provided to the 
animals; and, 
3. The heterogeneity of types of cells being accessed and 
provided to the animals. 
Dr. Mclvor said he believed the subcommittee would have to deal 
with two main issues: 
1. Do the data support a sufficient T and B cell 
responsiveness to warrant an attempt at therapy in 
humans at this point? 
2. Are the Milan and NIH protocols analogous enough to 
predict an efficacious outcome from the NIH protocol? 
Dr. Mulligan said he viewed the data from the perspective of 
whether it added anything to the existing data. He said the 
following issues were still difficulties in the protocol: 
1. Whether the T cell repertoire would be maintained, as 
was the case in the enzyme replacement approach; 
2. Whether culture conditions are good for preserving 
function of T cells and whether they are naturally IL-2 
responsive and what happens to them without growth 
factors; 
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Recombinant DNA Research, Volume 14 
