Recombinant DMA Advisory Committee - 09/14-15/92 
provided by lymphocytes, not tumor cells. 
Dr. Lotze agreed to omit the term "vaccine" from the protocol. Dr. Parkman suggested 
replacing this term with IL-4 transduced fibroblasts or simply cells. The reality is that 
the IL-4 transduced fibroblasts are functioning as an adjuvant, not a vaccine. 
Dr. Lotze responded to questions regarding the generation of adequate numbers of 
fibroblasts for each patient. He described the Hayflick phenomenon in which fibroblasts 
have a limited number of cell divisions. Although the number of possible generations is 
approximately 50, this number of fibroblasts is sufficient to provide for this therapy. In 
the event that a patient does not provide enough fibroblasts, he/she would not be 
eligible for this protocol. These patients may then be eligible for the tumor infiltrating 
lymphocyte protocol. 
In response to Dr. D. Miller's question, tumor cells will not be grown up for this 
experiment. The protocol specifies that tumor suspensions will be prepared from 
enzymatically digested primary tumors. The tumors will not be cultured. He agreed to 
submit the pertinent vector sequence information to ORDA. 
Dr. D. Miller asked if local administration of IL-4 would produce the same results as ILr 
4 transduced fibroblasts. Is delivery the problem? Dr. Lotze responded that a variety of 
vehicles exist for delivery of these agents. Experiments are now being performed to 
determine whether polyethylene glycol can be used as a delivery vehicle for ILA since 
this protein is not rapidly cleared. Dr. Parkman explained that a pump could be inserted 
locally; however, this pump may be a potential source of infection in these already 
immunosuppressed patients. Dr. Leventhal said that even if the investigators were 
successful at implanting a pump for secreting IL-4, it would be difficult to deliver 
identical amounts to different sites continuously. It would be impossible to interpret the 
results of such a dose-response experiment designed in this way. 
Committee Motion 
A motion was made by Dr. Parkman and seconded by Dr. Leventhal to approve the 
protocol contingent on: (1) submission and review of the vector sequence on a 3 Vi" 
diskette in ASCII format and (2) the term "vaccine" will be removed from the protocol. 
Dr. Murray called for a vote. The motion passed by a vote of 19 in favor, 0 opposed, 
and no abstentions. 
XIV. FUTURE MEETING DATE OF THE RECOMBINANT DNA ADVISORY COMMITTEE 
Dr. Murray noted that the next meeting of the RAC will be December 3-4, 1992. The 
meeting will be held at NIH, Building 1, Wilson Hall. 
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