Recombinant DNA Advisory Committee - 06/1-2/92 
Dr. Parkman stated that in order for the RAC to review the broad therapeutic aspects of 
a protocol, it needs the proper expertise. The RAC should only judge the subject matter 
for which it was constituted to review. The RAC should only receive copies of 
therapeutic protocols, not formally review these portions. The RAC should receive 
copies of the IRB reports. 
Mr. Barton moved to table Dr. Parkman's motion. The motion was seconded by Dr. 
Geiduschek. The motion to table was passed by a vote of 14 in favor, 5 opposed, and no 
abstentions. 
Other Comments 
Dr. D. Miller asked what animal model supports the use of this gene transfer technique 
in humans? There is extensive data from murine models by cocultivation of packaging 
cells with bone marrow cells for prolonged periods; the results in large animals have 
been dismal. Dr. Dunbar needs to expand on the primate data; specifically, to address 
cocultivation techniques versus supernatant infection. Supernatant infection techniques 
have not been successful in murine models. Dr. D. Miller asked about the persistence of 
stem cells in culture since they are missing the adhesion factors. The RAC should 
approve protocols only with valid animal support demonstrating that genes can 
successfully be transduced into CD34( + ) cells. 
Presentation~Dr. Dunbar 
Dr. Murray called on Dr. Dunbar to respond to the questions presented by the primary 
and secondary reviewers as well as the other committee members. Dr. Dunbar stated 
that the initial work in the primate system was tainted by the fact that there was helper 
virus contamination making interpretation of long-term reconstitution with marked cells 
difficult. Recent data exists that demonstrates a detectable level of gene marking can be 
achieved in a fraction of circulating cells in the bone marrow of monkeys that were 
transplanted with a helper free, clinically relevant system. 
In response to Dr. D. Miller's concerns about maintaining the reconstituting stem cells in 
culture under the defined growth factor conditions, Dr. Dunbar stated that these 
conditions are based on the murine system. Dr. Dunbar said that reconstituting stem 
cells have been successfully maintained and expanded using a combination of IL-3, IL-6, 
and recombinant human stem cell factor (SCF), noting that SCF appears to be the most 
critical component. There is ongoing research that indicates that human and primate 
progenitor cells can be expanded ex vivo using this system. In the animals that exhibited 
helper virus contamination, no delay in engraftment was observed; and there was no 
evidence that stem cells were damaged by the transduction and culturing procedures. 
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Recombinant DNA Research, Volume 15 
