Recombinant DNA Advisory Committee - 2/10-11/92 
Dr. Post questioned the safety of the protocol. Since the transduced cells were intended to 
persist, this persistence could increase the probability that a second insertional mutagenesis 
event could result in malignant transformation. The investigators stated that fewer 
numbers of cells will be transduced, thus reducing the chances for insertional mutagenesis. 
Dr. Post stated that there was little data on the proposed procedures for the amended 
protocol. In addition, there is a lack of data on the preclinical efficacy of the amended 
protocol. The original protocol used a different vector than this amended protocol. There 
is little information provided about the new vector in the proposed cell population. 
Further, there is no direct method for viewing ADA expression in CD34( + ) cells. 
Dr. Post asked whether the vector being used in this protocol, GlNa.SaVd, was the same 
one proposed in Dr. Economou's protocol except that SV40 ADA has been added. Dr. 
Post said if the vector is the same, that there were very informative details about this 
vector in the data submitted by Dr. Economou. Dr. Blaese stated that it was the same 
vector. Dr. Post asked if the reason for using this vector was to differentiate between the 
transduction of the CD34( + ) cells versus the whole T lymphocyte population. Dr. Post 
concluded saying that the investigators could answer his questions without referring the 
protocol back to the HGTS. 
Review-Dr. Krogstad 
Dr. Krogstad stated that many of his comments were similar to Dr. Post's, and that he was 
impressed by the rationale for these studies. Dr. Krogstad recognized the potential of 
long-term correction and has spoken with Dr. Anderson about this vector. There are 
several issues that need to be addressed: (1) marking of CD34( + ) cells; (2) the expected 
numbers of CD34( + ) cells in ADA deficient children; (3) presence of antibody attached to 
the cells completely removed prior to reinfusion; and (4) detailed information concerning 
PCR markers. Dr. Krogstad noted the possibility that enhanced or different toxicity might 
be observed with two retroviral vectors instead of one. 
Dr. Krogstad said that he had two minor concerns about the consent form: (1) a 
statement should be added that gene corrected cells may or may not be as effective as 
BMT; and (2) the statement "this protocol might not be useful for children who live too far 
away to travel frequently to the NIH Clinical Center" should be omitted. Dr. Krogstad 
concluded that he was in favor of approving this amendment. 
Review-Mr. Capron 
In Mr. Capron's absence, Dr. Post presented his comments. Mr. Capron had concerns 
about whether this protocol should go before the HGTS; however, he concluded that the 
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