July 30, 1990, Human Gene Therapy Subcommittee 
Dr. Rosenberg said that, since the patients to be selected for the protocol will have 
clearly evaluable disease, any antitumor effects would be carefully noted and measured 
during the course of treatment of the patient. He reiterated that the protocol is a Phase 
I protocol and not a Phase II protocol and that the protocol was not designed to evaluate 
efficacy, merely to note it when and where possible during a short duration experiment. 
He added that, if the effects were dramatic, they would see them. 
12. How was the TNF level of 150 picograms per 10^ cells per day minimum 
level of transduced TIL determined? 
Dr. Mclvor said this question was addressed. However, he thought that the numbers 
must be interpreted to give the system the benefit of the doubt in order to come up with 
a positive prediction. It is important to know the TNF concentration at the level of 
expression of the cells, at the level of homing, and also at the level of how much 
interstitial space secretion will be observed. It would be important to know if there is 
lack of diffusion of TNF from the site. 
Dr. Mclvor said that since this was a Phase I toxicity study of the administered TILj^f, 
the major consideration should be the determination of anticipated toxicity. He was 
disappointed by the lack of animal data relevant to the system as proposed. He said the 
predictions show this dose to be safe, in light of observed human data, despite some 
questions as to differences in the maintained level of TNF and the pharmacokinetics of 
TNF expressed from the infused TIL cells. 
Dr. Leventhal made the following suggestions for the protocol regarding toxicity. She 
said: 
1. That under "Parameters to be Measured," precise indications of frequency 
of collection of toxicity data were needed; 
2. That "Appendix B" shows the type of toxicity data that is to be collected; 
however, no frequency of data collection is noted; 
3. That she did not understand what "Bronchospasm - no parenteral therapy 
required" represented; 
4. That a space be left on the form to indicate dosage being administered; 
5. That anything reported as grade 4 toxicity will be reported as adverse 
toxicity; however, the protocol does not clearly state that higher grades will 
be annotated; 
6. That the "Statistics" section implies that only one patient will be used at a 
Recombinant DNA Research, Volume 14 
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