Human Gene Therapy Subcommittee - 7/30/90 
patient toxicity, as well as possible therapeutic effects, will 
be noted." He asked if these therapeutic effects were meant to 
be those specifically attributed to TNF, or just overall 
therapeutic effects. 
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 picogreuns per 10^ cells 
per day minimvim 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 TIL^jjp, 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; 
Recombinant DNA Research, Volume 14 
[87] 
