Hvunan Gene Therapy Subcommittee - 7/30/90 
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 
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Recombinant DNA Research, Volume 14 
