Recombinant DNA Advisory Committee - 03/1-2/93 
salvage therapy with 5-fluorouracil (5-FU) and other chemotherapeutic agents, which are 
not MDR pump drugs; therefore, their effectiveness would not be affected by MDR gene 
transduction. 
Dr. Carmen explained that he had been assigned as a primary reviewer of Dr. Bank's 
protocol before it was withdrawn for review from the September 1992 RAC meeting. 
How does the current protocol differ from the previously submitted protocol other than 
the fact that ovarian cancer is no longer the targeted disease? What is the status of the 
murine immunodeficiency model? Dr. Carmen then submitted suggested language for 
inclusion in the informed consent document. 
Dr. Post noted that the proposed vector includes 6 additional kilobases which are 
upstream from the MDR cDNA What are these additional sequences? Does it make 
gag? Are any additional retrovirus proteins made? Does this MDR vector have the 
same point mutation and frame shift that Dr. O'Shaugnessy's vector had? What is the 
status of characterizing the performance of this vector in the proposed packaging cell 
line? What is the status of Institutional Review Board (IRB) approval of this protocol? 
The RAC received a document which granted approval in principle; what are the 
specifics of approval? 
Dr. Leventhal stated that all investigators submitting human gene transfer protocols to 
the RAC should grow and/or purify the target population of human cells and transduce 
these cells with the same vector proposed for the study. There is no data demonstrating 
that purified human CD34( + ) cells have been transduced with the proposed vector. 
Since the target cell population exhibits MDR expression, which decreases as the cells 
mature, the investigators must demonstrate that the transduced CD34( + ) cells express 
higher levels of MDR than the cells produce spontaneously. What is the effect of 
transduction? 
Dr. Geiduschek stated his concern about the quantitative expression of MDR in the 
transduced population. The investigators have not submitted data to address the critical 
question, namely, a comparison between Taxol-selected transduced and untransduced 
cells. Does Taxol selection cause an increase, decrease, or sustained expression of 
MDR? The section of the protocol that describes the CD34( + ) selection procedure 
should be clarified. The investigators propose that 30-50% of the total number of bone 
marrow cells harvested will be removed for CD34( + ) selection, depending on the total 
cell harvest yield. What factors will influence this percentage? The following statement 
needs to be clarified by the investigator: "We will evaluate the safety of gene transfer by 
looking for the presence of intact retrovirus in the bone marrow; this is the major risk." 
The presence of intact retrovirus would be for only a brief duration. Are there other 
parameters that will be used to monitor the safety of this procedure in patients? 
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Recombinant DNA Research, Volume 17 
