Human Gene Therapy Subcommittee - 7/30/90 
3. How much tumor accumulates in the TNF tumor-transduced 
mice, and how much TNF is expressed in vivo ? 
Dr. Mclvor said the tumor studies in mice demonstrated the 
specificity and role of TNF in mediating regression of tumors 
that are expressing TNF. But he said he was unclear as to 
exactly how much tumor accumulates and how much TNF is secreted 
in animals that have had tumor cells administered. 
Dr. Rosenberg said that he could not answer the question in an 
exact amount, but that a 4 millimeter tumor would contain a very 
large amount of TNF compared to what the TIL will make before 
tumor regression. Dr. Mclvor said that this would equate to 
about a milligram per day. Dr. Rosenberg said that this was 
true, but the TNF has a very short half-life and the tumors don't 
last long and begin to regress after about 10 days. 
4. In the TNF-TIL infused monkeys were comparable numbers 
of cells infused? Were the expression levels the same? 
Is IL-2 being administered and at what level? 
Dr. Mclvor said that, since data indicate that removal of IL-2 
results in a lack of survival of TILs, he wondered if the cells 
would survive in the monkey at all, and what this means in terms 
of the assessment of toxicity in the monkey experiments. 
Dr. Rosenberg said that a main limitation of the monkey model is 
that the cells are human cells in an immunosuppressed monkey. He 
said he did not believe the human cells were likely to survive as 
long in the monkey as in humans. But he emphasized that the 
amount of TNF made by LAK and TIL which do survive in the 
presence of IL-2 is higher than the starting dose proposed in the 
protocol. Thus, the investigators do not see this as being a 
major problem. 
Dr. Mclvor asked if the monkeys could be given IL-2. Dr. 
Rosenberg said it would be a major effort to do this. However, 
he said it potentially could be done. He said his feeling was 
that, since humans had already tolerated higher doses of TNF made 
in TIL and LAK cells, it was not necessary to perform yet another 
safety study. 
5. Does IL-2 withdrawal result in a drop in TNF-TIL in 
vivo , and in serum TNF? 
Dr. Mclvor said this question was answered in the response to 
question one. 
Recombinant DNA Research, Volume 14 
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