Recombinant DNA Advisory Committee - 06/1-2/92 
Although this level may be higher, it will not be less that 150 picograms. The highest 
producing clones will be used for injections. 
Dr. Brenner addressed Dr. D. Miller's question regarding the possibility of IL-2 retroviral 
rescue. Dr. Brenner said that he was unaware of any evidence that such rescue has ever 
been reported. Dr. D. Miller noted animal model data published by other investigators 
indicating that cytokine genes produced at the time of bone marrow transplant result in 
leukemias. Dr. Brenner stated that the experiments Dr. D. Miller referred to were 
performed with bone marrow cells. Dr. Brenner explained that since the protocol is 
designed to insert the gene coding for IL-2 expression into tumor cells, the 11^2 
retrovirus would have to be rescued from the tumor cell into the T cell. 
Dr. D. Miller asked Dr. Brenner if he had performed animal experiments in which T 
cells have been removed from the animal, transduced with this IL-2 retrovirus, and 
readministered to the animal. Dr. Brenner said that he has not performed bone marrow 
transplant experiments with this vector, only transduced tumor cells. 
Dr. D. Miller asked Dr. Brenner if data exists regarding autonomous growth of T cells 
resulting from the administration of cytokine producing tumor cells. Dr. Brenner said 
that he was not aware of any data which indicated this occurrence. Dr. Culver noted 
that his laboratory has used this same vector and inserted it into mouse sarcoma cells 
that were virus-induced. In turn, these cells were implanted into mice. The tumors were 
rejected, and there has been no evidence of malignancy, either hematologic or otherwise. 
Dr. D. Miller suggested that perhaps this information should have been submitted as 
relevant data for this protocol. Dr. Parkman suggested that Dr. D. Miller's question is 
independent of this particular vector. If you introduce this vector into a cell line and 
infuse this cell line into an animal, is there any evidence that the vector will be 
transported into the somatic cells of the animal? If transfer to somatic cells does not 
occur, the issue of vector transport is inconsequential. 
Dr. D. Miller noted that this data was generated using a murine model. Mice activate 
endogenous viruses, particularly in tumor cells. He has not seen data that demonstrates 
that neuroblastoma cells do not produce human helper virus that can rescue and transfer 
the vector. He asked Dr. Brenner if he had data regarding the production of human 
helper virus from neuroblastoma cells. 
Dr. Brenner responded that he has approached these experiments from several angles. 
He stated that there has been no evidence of rescue among human systems or that the 
IL-2 retrovirus has oncogenic potential. 
Dr. Leventhal asked the investigators if they will remove T cells from these patients after 
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