Hvunan Gene Therapy Subcommittee - 7/30/90 
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 
investigators are interested in obtaining both infection of cells 
required for successful engraftment to keep the patient alive and 
malignant cells potentially to be found in the bone marrow 
inoculum. He said that transduction protocols must be considered 
within the framework of the ABMT therapy and that transduction 
should neither interfere with the ability of the bone marrow 
cells to reconstitute, nor increase the frequency and/or growth 
potential of any tumor cells in the marrow sample. 
Dr. Mulligan said that feasibility studies needed to be 
elaborated in more detail, particularly with respect to assays to 
be employed in assessing effects of specific culture conditions 
on progenitor and tumor cell growth. Further, he said the 
investigators need to clarify in more detail what successful 
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Recombinant DNA Research, Volume 14 
