Human Gene Therapy Subcommittee - 11/30/90 
expanded them in order to study them. Further, there was the issue of what might 
happen in normal hematopoietic progenitor cells. This proposal did not fulfill these 
same criteria in that the only evidence presented was that the investigators could 
infect neuroblastoma cell lines. In many patients, so many cells are non-cycling that 
it is impossible to grow cell lines in vitro. If these patients relapse, there would be 
no way to grow cells to study clonality, which would result in repeating the same 
hematological studies described in the previous protocol. Therefore, more 
preclinical studies need to be performed with the neuroblastoma cell line to assure 
that the vectors can be introduced into the target cells so that if relapse occurs, it 
can be assessed in such a way as to produce good scientific information. 
Dr. Brenner said that the objectives of this study were more limited than those in 
the previous protocol. A reasonable transduction frequency as measured by limiting 
dilution analysis or direct staining in 16 different cell lines would be obtained. This 
result did not mean that primary tumor would stain with the same efficiency. The 
efficiency of transduction is unknown. There is a reasonable chance that the 
investigator will be able to detect marked cells in the marrow of patients that 
relapsed. The question is whether or not this chance is sufficient to justify the 
procedure. 
Dr. Brenner said the potential benefits of discovering whether or not purging will 
improve survival, and what approaches to purging should be taken outweighed the 
risks to the patient. Currently, 75% of patients with this disease relapse within three 
years; and they die rapidly. 
Dr. Mclvor asked if these tumors could be grown in animals. Dr. Brenner said that 
such studies were possible, but that the investigators had no advantage over growing 
the tumors in cell culture where most of the tumors die out, and what remains is a 
cell line with a selected cell population. 
Dr. Kelley asked whether it would make more sense to focus efforts on the previous 
protocol in light of the difficulties with this protocol and to hold the current protocol 
in abeyance until results of the previous protocol can be assessed. Dr. Brenner said 
that these dealt with different diseases; the information gained from one protocol 
will not really reflect on what is gained from the other protocol. 
Dr. Kelley said that information as to differences in techniques may accrue via the 
first protocol; this information could be helpful in assuring a more positive result in 
this protocol. Dr. Brenner said that plan would be reasonable if marking of normal 
progenitors were the principal aim. Since AML and neuroblastoma have different 
biological behaviors, there is a question of what knowledge would be gained. 
Recombinant DNA Research, Volume 14 
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