Human Gene Therapy Subcommittee - 7/30/90 
be made available in an emergency if FDA were willing 
to let it be used in humans. 
Dr. Rosenberg said he believed he had covered all the areas in 
question and said he would be happy to answer any other 
questions. 
Dr. Walters thanked Dr. Rosenberg and suggested the subcommittee 
take its luncheon recess and reconvene promptly at 2:00 p.m. for 
continuation of the discussion of this protocol. 
Dr. Walters reconvened the subcommittee at 2:05 p.m. He noted 
additional comments had been received and distributed to 
subcommittee members from Mr. Alexander Capron in relation to the 
protocol and from Dr. Brigid Leventhal on the protocol of 
Drs. Brenner, et al., from St. Jude's Hospital. He reminded the 
subcommittee that there was a third protocol to be discussed 
during the meeting and suggested that this fact be kept in mind 
by the members. Dr. Walters then called on Dr. Mclvor to 
summarize the issues of the protocol under discussion and to 
identify where each issue currently stood in light of Dr. 
Rosenberg ' s presentation . 
Dr. Mclvor said he would go over, point by point, each item he 
had mentioned in his initial review. 
1. Do the TNF-TIL maintain their IL-2 dependence after 
infusion? 
Dr. Mclvor said this issue had been removed from consideration by 
the evidence presented that once IL-2 is removed, it is not 
possible to detect retroviral sequences. He asked if there were 
any in vivo data on experiments such as this which had been done 
with TNF-transduced TIL. Dr. Rosenberg said such cells hadn't 
been given to patients and that the question was unanswerable 
except by carrying out the experiment in humans. 
2. Does the 8 mg/kg/day toxicity level pertain to a single 
injection or to a continuous infusion? If both, how is 
this explained, considering that TNF has a half-life of 
5-10 minutes? 
Dr. Mclvor said the presentation had answered a lot of questions 
about what the exact toxic level was and the routes of 
administration, but added that it was still difficult to predict 
what difference may be seen in infusion and expression from a 
cellular source rather than an extracellular source. 
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Recombinant DNA Research, Volume 14 
