July 30, 1990, Hunan Gene Therapy Subconmittee 
4. Will there be a back-up marrow source? 
She said the plans for the possible use of growth factors are sketchy. Further, specific 
growth factors may stimulate the growth of tumors as well as normal marrow cells. She 
said any such studies should be spelled out in great detail and considered individually by 
tumor type and growth factor combinations. 
Dr. Leventhal said she had the following questions about the design of the study: 
1. How will it be possible to determine what cells are labeled in vitro when 
there is no detectable tumor at the time of harvest? 
2. Have mixing studies been done? 
3. Is there a reason to think that transfection of tumor cells will be selective 
vis-a-vis normal marrow stem cells? 
4. How is it possible to determine which cells have been transduced once the 
procedure is complete? 
5. What are the procedures for searching for a transfected cell after 
transplantation and reconstitution? Is it possible to determine which cell 
has the vector at that point? 
Dr. Leventhal said that feasibility studies need to be done and calculations made 
concerning how many patients are required to have a meaningful study. She added that 
with some preliminary data it may be possible to be more precise in estimating levels of 
labeling to be anticipated to allow for better estimates of the number of patients needed 
to perform the study. She said that specific goals should be stated in as quantitative a 
fashion as possible. 
Ms. Meyers asked if any preclinical work has been done in monkeys and, if not, why it 
shouldn't be done in monkeys before attempting to go to human beings. Dr. Leventhal 
said that since the vector being used is the neo vector, which is safe, the only question 
remaining is whether the marrow will regrow after treatment. If it doesn't regrow, then 
the experiment is not safe. However, monkeys do not have the same kinds of tumors as 
humans and a beautiful experiment in monkeys could be irrelevant to human oncology. 
Dr. Mulligan said he had similar views about the proposal. He noted the protocol was 
logical, well written and addresses a key problem. He said, while most of the issues 
regarding use of retroviral mediated gene transfer were addressed in previous protocols, 
this protocol sought to transduce and transplant different populations of hematopoietic 
cells than have been previously infected and transplanted. Further, he said that the 
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