Recombinant DMA Advisory Committee - 5/30-31/91 
Dr. Anderson said that as far as ADA in the blood stream was concerned, the patient was 
now up to roughly 20 percent of normal. He said that PCR analysis showed approximately 
the same insofar as fraction of ADA-positive cells, that is 20 percent, but that this leads to a 
concern that as she continues to increase the percentage of gene-corrected cells had has a 
higher and higher percentage of these cells that by taking cells out every month and adding 
the additional ADA gene to them that they will indeed begin to add second and third genes 
to cells which already possess the ADA gene. He said the investigators were looking into 
ways of trying to pan out cells that are already corrected from the pool being taken out so that 
they only are correcting cells which do not possess the ADA gene. He noted further that once 
50 percent of cells contain the ADA gene the investigators intend to stop and wait and see 
how long she can then go on her own without further infusions. 
Dr. Miller asked if there was any evidence of antibodies to ADA or neutralizing antibodies 
in the patient. Dr. Anderson responded by noting that there is no such evidence yet, although 
the patient is making CRM (cross-reactive material) and therefore there is some evidence that 
she is making something. 
Dr. McGarrity asked if the investigators could distinguish between the PEG- ADA and the 
recombinant ADA in the patient. Dr. Anderson said this was easily distinguished since the 
PEG- ADA is a bovine preparation and it was only found in the circulation. 
Dr. Miller asked if the investigators contemplated withdrawal of PEG-ADA as they had 
originally considered. Dr. Anderson said the intention was to give the patient at most 3 more 
infusions and then to stop and follow her for a period of time and do a complete immune 
analysis. If the gene-corrected cells continue to have a selected growth advantage then the 
investigators will submit Part III of the protocol to the RAC for review since it would be at 
least a year before they would consider removing the PEG-ADA from the patient. However 
he voiced concern that they may not be able to remove the PEG-ADA due to safety concerns 
as to whether she can maintain herself in a fully detoxified state with only 50-60 percent of 
T cells making ADA. He said that if, after removal of PEG-ADA, there were any danger at 
all she would be put back on the PEG-ADA. 
Dr. Walters asked how Dr. Anderson would respond to the possibility that the therapeutic 
benefit being seen in the patient thus far was primarily due to the large number of T cells that 
were being infused in her, rather than the genetic modification. Dr. Anderson said that there 
was a flaw in the protocol in that there is no control to assess this. He noted that in order 
to control for this it would be necessary to do exactly the same protocol but to put in the 
LNL6 gene instead of ADA and see whether she was helped just as much by simply having 
her T cells grown up and returned to her. However, he said he did not believe this to be 
ethical in that the investigators have always felt that in theory the best bet to achieve success 
would be to correct the defective T cells so that they became normal T cells. He noted that 
time would give the appropriate answer but that the investigators felt from a clinical point of 
view this was a control which they did not wish to undertake from this ethical viewpoint. 
Recombinant DNA Research, Volume 14 
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