Recombinant DNA Advisory Committee - 7/31/90 
After the coffee break, Dr. McGarrity said that some work had 
been done on the consent form. He asked Dr. Epstein to summarize 
what had been accomplished. 
Dr. Epstein said that the group had specific wording worked out 
as to the first couple of paragraphs of the consent document. 
This incorporated all the concerns that were expressed, as well 
as additional changes to be made in the organization to include 
TNF toxicity. He said the group was satisfied with what had been 
developed. 
Dr. Walters said the language that was drafted states the purpose 
of the TNF element of the current study clearly, and the group 
agreed that it would be wise to break this out as a separate 
section in the consent form, resulting in separate sections for 
IL-2, TIL cells, and TNF. 
Dr. McGarrity asked for other comments on the consent document. 
There being no further comment, he asked for questions or 
comments on the remainder of the protocol. 
Dr. Schaechter said he wished to see more discussion of the issue 
of safety. In particular, he wanted to hear more detail on the 
question of what can be expected from the introduction of 
genetically modified cells in terms of over expression and the 
ability to intervene with removal of IL-2, as well as treatment 
with steroids and antibodies to shut down over-production of a 
toxic dose of TNF. 
Dr. Mclvor once again stressed that the predictions of safety 
were based on in vitro experiments, and there may be a difference 
in level of expression in vivo, which could lead to an enhanced 
toxic effect. The only way to determine whether this will occur 
is to perform the experiments in vivo. Furthermore, the only in 
vivo data was provided from a study in monkeys in which IL-2 was 
not co-administered. Therefore, such data is not totally 
analogous to the study being proposed. Some questions do exist 
about the potential for a toxic effect in this protocol. 
Dr. Rosenberg said that there are four lines of evidence that 
support the selection of the starting dose: 
1. The starting dose of cells to be used produces less 
than 1 percent of the TNF per day tolerated by humans 
following intravenous infusion; 
2. Up to 6 X 10^^ TIL, which make TNF in low amounts, have 
been given to human patients and the total amount of 
TNF made by those cells is in substantial excess to 
that of the starting dose proposed of TIL,pjjp; 
Recombinant DNA Research, Volume 14 
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