Human Gene Therapy Subcommittee - 7/30/90 
Dr. Mulligan asked if Dr. Bordignon had an estimate of the 
frequency of the initial fraction of cells that are infected in 
his experiments. Dr. Bordignon said that this is not known but 
is being studied currently. 
Dr. Mclvor asked if any ADA assays had been done on the bulk 
population after infection. Dr. Bordignon said it was between 
1/5 and 1/3 of what would be expected with a good expression 
clone after 2 days of integration and expression time. 
Dr. Herschfield asked if it would be worthwhile to maintain the 
ADA-deficient cells from the patient in the presence of a level 
of PEG-ADA or other exogenous concentrations of ADA while they 
are in vitro or after injection into the mice. Dr. Bordignon 
said that he had done a variation of this experiment and that it 
did not affect response to antigens or PHA proliferation. Dr. 
Herschfield asked whether most of the deoxyadenosine that the 
cells are exposed to didn't come from degradation of DNA by 
macrophages, with red cell precursors being the source of the 
DNA. Having ADA outside the cells that are ADA deficient could 
allow them to function or persist for a longer period of time 
once removed from the patient. Dr. Bordignon said this was 
possible. 
Dr. Walters thanked Dr. Bordignon for his cooperation in 
attending the meeting and presenting his data. He then asked Dr. 
Parkman if he had any further points to make relative to the i.p. 
route of administration in light of Dr. Bordignon 's data. 
Dr. Parkman said he was not comfortable with leaving the decision 
for instituting i.p. administration up to the local IRB. He 
thought that it should either be removed from the protocol 
altogether or that the investigators be required to return to the 
HGTS with data showing a greater level of efficacy with the i.p. 
as opposed to the i.v. route. 
Dr. Anderson said he did not feel this process was necessary if 
the investigator and all of the IRBs who will have to approve 
such a change in the protocol felt it was in the best interest of 
the patients. It would cause undue delay because of the 
frequency of the HGTS meetings. He asked for a compromise of 
having it come before a small subgroup of the subcommittee for 
approval similar to the "chairman's approval" of minor 
modifications in protocols. Dr. Blaese said the reason he left 
this option in the protocol related to concern over how children 
would tolerate repeated i.v. infusions. He was concerned that if 
the treatment appeared beneficial, but was resulting in systemic 
reactions, he wanted to leave the i.p. administration as an 
Recombinant DNA Research, Volume 14 
[73] 
