July 30, 1990, Human Gene Therapy Subconmittee 
1. Stop giving IL-2, because the cells are dependent on ILr2 for survival; 
2. Administer steroids which have a lymphocytic effect in humans which 
should cause lysis of any cell which survives H^2 withdrawal; and, 
3. Administer anti-TNF antibody. Dr. Rosenberg noted that several 
commercial firms are now aggressively pursuing techniques to produce anti- 
TNF antibody and that enough should be available by the time it is needed 
and could 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 TIIv^nf 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 lL-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? 
[192] 
Recombinant DNA Research, Volume 14 
