Recombinant DNA Advisory Committee - 7/31/90 
Dr. Gellert noted that this had been inserted on pages 61 and 62 
of the revised protocol. 
Dr. Gellert said the only two issues to consider were the consent 
form and the data from the Milan experiments. He noted that Dr. 
Bordignon had made a presentation to the HGTS on July 30, 1990. 
He said Dr. Parkman could also discuss this, but Dr. Gellert made 
the following comments relative to this presentation. 
Dr. Gellert said Dr. Bordignon 's data showed that infusion of 
cells from a child with ADA deficiency into immunodef icient mice 
would be unsuccessful if the cells were not treated. However, if 
a vector carrying the ADA gene were inserted into the human ADA 
deficient cells, the cells would survive in a relatively 
equivalent fashion to immune cells from a normal patient. 
However, if a patient has been previously immunized with tetanus 
toxoid, then among the ADA-containing cells, one can detect a 
tetanus toxoid response, after passage through the mouse. He 
said the problems with this model were twofold. One, the cells 
came from a patient who had been on PEG-ADA therapy, and who 
would have been too well from the standpoint of immune 
reconstitution to be eligible for the proposed protocol. Two, 
the ADA-containing vector was not the same one that is being 
proposed in the protocol. Therefore, there are two possible 
models proposed for how this therapy might work: 
1. ADA-containing lymphocytes may survive longer; or 
2. ADA-containing cells may detoxify the environment to 
make the endogenous immune system in the patient 
function in a more normal fashion. 
Dr. Gellert noted that the Milan data supports the first 
hypothesis but sheds no light on the second. However, despite 
these imperfections in the preclinical model, the HGTS felt this 
was promising enough evidence to vote in favor of the proposed 
protocol . 
Dr. McGarrity called on Dr. Childress for his comments. Dr. 
Childress said he would elaborate on the discussion of the 
consent form. He said the discussion centered on the need for a 
stronger warning about risks of malignancy and other unknown 
risks. He said the revised consent and assent forms were an 
improvement. He stressed the helpfulness of the organization, 
the addition of headings, and appropriate expansion and clarity 
of writing in the new forms. Additional specific changes were 
recommended, mainly for clarification, and he said he would be 
happy to reply to questions about these. 
Dr. Childress said suggestions from Ms. Meyers and Dr. Leventhal 
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