Recombinant DNA Advisory Committee - 7/31/90 
3. LAK cells have been given to almost 200 patients now. 
These cells make substantial amounts of TNF (500 
picograms per 10^ cells per 24 hours) and they are 
cleared in a method similar to that of TIL,pjjp; and 
4. Monkey studies have been performed to control for the 
initial toxicity of giving the cells. 
Dr. Schaechter asked for more information on ameliorating 
toxicity with removal of IL-2, administration of steroids, and 
use of anti-TNF antibody. 
Dr. Rosenberg said that over 800 patients had been treated with 
high dose IL-2, with or without cells. In every case when IL-2 
is removed, the side effects dissipate. The cells are checked 
beforehand to ensure they die in the absence of IL-2, and they 
would not be given to a patient if this were not the case. 
Secondly, Dr. Rosenberg said if there is severe toxicity due to 
the TNF, 4 milligrams of dexamethasone will be administered every 
6 hours for 48 hours. This has a substantial anti lymphocyte 
effect in man and should remove almost all detectable 
lymphocytes. Furthermore, in conjunction with cessation of IL-2, 
it should be very effective in ameliorating toxicity. 
Thirdly, Dr. Rosenberg said his group is working hard to obtain 
anti-TNF antibodies. These have been shown in non-human primates 
to abrogate the effects of endotoxemia which leads to TNF 
production. He said anti-TNF antibodies are not commercially 
available at the present time but that Cetus Corporation is 
working on one that could be used in humans. Dr. Rosenberg's 
group is working closely with them to ensure its availability 
should the need arise. It would require FDA approval before use. 
Dr. R. Murray asked if there were a precedent to believe that in 
vivo expression of a particular element in cells might surpass in 
vitro expression, or whether this was purely hypothetical. 
Dr. Rosenberg said such a phenomenon had not been seen with TIL. 
In fact, the opposite seems to be true, that in vivo they die 
more quickly and are cleared. Dr. Anderson reiterated this point 
and said that the real problem would relate more to efficacy 
rather than safety due to the rapid clearance in vivo. 
Dr. Krogstad asked what was the amount of antibody needed to 
neutralize biological effects of the TNF toxicity and how that 
compares to how much is currently available. Dr. Rosenberg said 
anti-TNF antibody is not available yet, but realistically he felt 
enough could be made available to do the job. 
Mr. Brewer asked what effect the withdrawal of IL-2 in the case 
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