Human Gene Therapy Subcommittee - 11/30/90 
Dr. Parkman said that investigators may not be able to insert the virus into the cells 
and asked that further experiments be conducted to show that an unselected cell 
population with a primary infection yielded transduced cells. More preclinical data 
is necessary to suggest that the experiment could produce positive results. 
Dr. Erickson moved that the HGTS defer approval of the protocol, pending receipt 
of additional preclinical data. Mr. Capron seconded the motion. 
Dr. Anderson noted that a deferral would mean the protocol could not start until 
June. Dr. Parkman said it would take at least that long to develop the data 
necessary to convince the HGTS that the protocol had a reasonable chance of 
succeeding. 
Dr. Kelley asked if the HGTS would expect the same kind of information on this 
protocol as was supplied in the AML protocol. Dr. Parkman said that the 
information would be more limited because of the difference in the biology of the 
disease. It should be as parallel as possible, looking at the infection of marrow 
samples that contain neuroblastoma cells, and then trying to grow out the clonigenic 
cells. Realizing the cells are not really clonigenic, but simply growing out the cells 
that are capable of growth in vitro and looking at whether the cells contain the virus 
or gene that was introduced. 
Dr. Anderson asked how easy it would be to conduct these experiments. Dr. 
Brenner said that it would be difficult because cells obtained from most patients do 
not result in the formation of cell lines. It would take a large number of patients to 
get enough neuroblastoma cells that would survive in vitro. Such an experiment 
could take years. If a short-term transfection was suitable, then that would be a 
different question. He said he was unclear as to how much knowledge would be 
gained from knowing that cycling cells can be transduced. The reason for using a 
dual protocol was to assure that the risks were kept to a minimum. 
Dr. Parkman said that the HGTS is more concerned with the ability to answer the 
scientific questions being asked than with the issue of risk. Dr. Brenner asked 
whether primary infection was sufficient or whether it had to be a long-term in vitro 
line. Dr. Parkman responded that it was up to the investigator to determine when to 
return to the HGTS with the data; but at this point, there were no data on primary 
neuroblastoma cells. 
Dr. Mclvor suggested that since the neuroblastoma cells can be sorted and the 
investigator has a beta-galactosidase vector available, he could infect the marrow and 
then sort for neuroblastoma and stain for beta-galactosidase. Dr. Mclvor said this 
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Recombinant DNA Research, Volume 14 
