Recombinant DNA Advisory Committee - 12/2-3/93 
proposed. LgGC has been safety modified to reduce the risk of RCR. The investigators 
propose to use a new packaging cell line, PG13, to enhance gene expression. Preclinical 
safety testing data has not been submitted for this LgGC/PG13 system; however, the 
investigators note that similar data was not required for approval of Dr. Barranger's 
protocol of Gaucher's disease. Dr. Carmen recommended that the RAC maintain 
consistency in its review and approval of similar protocols. If accelerated review is 
adopted by the RAC, this protocol is an example of experiments that may qualify. In 
this particular situation, the onus would be on the investigator to provide satisfactory 
preclinical safety testing data for the new vector. He submitted several 
recommendations to the Informed Consent document to make the document more 
understandable to laypersons. 
Other Comments 
Dr. Parkman noted his intention to abstain from voting on this protocol due to conflict 
of interest (participated in a similar protocol at the University of Southern California). 
He commented that there may be a benefit to having 3 simultaneous trials for the same 
disease but utilizing 3 slightly different vector constructs. Biologically relevant 
information would be obtained in a shorter time frame. He expressed concern about 
whether data is conclusive about GC expression in hematopoietic stem cells, despite 
demonstration of such expression in other cell types such as fibroblasts. Dr. Haselkom 
expressed concern about Dr. Schuening's inability to obtain adequate levels of GC 
expression using one of the other vectors previously approved by the RAC. Dr. 
Haselkom noted that it was important for the Pis of these similar trials to maintain 
communication with other investigators about scientifically relevant data. Ms. Grossman 
stated that perhaps the investigators' failure to reproduce previous experiments is due to 
lack of experience with particular techniques. Dr. Parkman explained that expertise is a 
key element that must be considered especially when the RAC begins to consider multi- 
center trials. Investigators must demonstrate successful transduction even when the same 
vector and target cells are proposed. 
Dr. Post asked the investigators to provide additional information about RCR testing of 
the LgGC/PG13 system. A new env gene has been introduced into this system. 
Investigator Responses--Dr. Schuening 
In response to the RAC's concerns about the choice of vector, Dr. Schuening said that 
he has collaborated extensively with Dr. Barranger on these preclinical studies. In 
regard to the issue of the optimal vector for stem cell transduction, the human clinical 
trials will most adequately address this question. Both the MFG-GC vector (used by Dr. 
Barranger) and the LgGC vector yield similar results with regard to in vitro transduction 
of human progenitor cells. Dr. Schuening clarified an earlier statement about the 
inability to reproduce similar levels of GC expression with Dr. Karlsson's vector. He was 
referring to the transduction experiment in which stromal monolayers were employed to 
maintain long-term repopulating cells. No patients have been accrued onto Dr. 
Karlsson's previously approved protocol because he is awaiting FDA approval. Dr. 
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