July 30, 1990, Human Gene Therapy Subconmittee 
a protocol be brought back that was more focused, with more preclinical data showing 
the investigators ability to insert the retroviral vector into neoplastic target cells. 
Dr. Leventhal suggested that the bone marrow manipulations be performed before 
purging. She said this might increase the number of labeled cells that could be extracted 
from the marrow. She asked if there was a real concern about whether growth of 
normal marrow stem cells might be suppressed by the manipulations being performed 
and whether there was evidence for selective labeling of tumor cells relative to normal 
stem cells. She suggested these questions could be answered by in vitro experiments. 
Further, she said that the performance of more studies in vitro could help to refine 
techniques for identification of the cell of origin for viral DNA found post-transplant. 
Dr. Mulligan asked if there was any proof that cells could reconstitute after being in 
culture for any length of time and whether it would be possible at all to get 
transplantation of these cells. 
Dr. Walters called on Dr. Brenner to address the concerns of the reviewers and other 
subcommittee members. Dr. Brenner said the reason that three different groups of 
patients were chosen was that each group would answer a different type of question and 
that all the questions could not be answered with a single patient group. He said the 
AML group would answer the question of whether the malignancy derives from a 
marrow multipotent cell or a committed cell, and would have implications for future 
treatment. He added that there was no evidence that purging would have any impact on 
stem cells or very early progenitors of either malignant or normal cells. He said there 
was no reason to believe that transfection frequency or transduction frequency would be 
altered, although that is something which this experiment would seek to elucidate. 
Dr. Brenner said the neuroblastoma studies would not have the same criticism leveled at 
them since no purging would take place. He said they are interesting because they are 
not hemopoietic malignancies and are not responsive to the kind of hemopoietic growth 
factors that AML is. The goal of this portion of the study is to determine the source of 
the relapse and to test response of cells to growth factor, in particular IL-3. 
He said that in the glioma patients the interest is to see whether it is possible to 
transfect and transduce non-cycling marrow cells and what impact growth factors such as 
IL-3 have on these patients. 
Dr. Leventhal asked how it was going to be possible, after transplant, to determine the 
source of relapse and whether a particular cell was a result of residual tumor in the 
transplanted cells or a residual cell in the marrow. Dr. Brenner said this could only be 
done if there were a multiplicity of cells which contribute, in which case some cells 
would be marked and others not. 
Recombinant DNA Research, Volume 14 
[205] 
