Human Gene Therapy Subcommittee - 7/30/90 
However, he said there were no known cytokines circulating in 
patients that receive TNF, and it is measured as part of their 
ongoing studies. 
Dr. Mahoney asked if perforation of the gut was a prominent side 
effect of IL-2 toxicity and, if so, whether IL-2 might stimulate 
infused cells which traffic to places such as the gut wall to 
secrete necrotizing substances. Dr. Rosenberg said that only 
four cases out of 900 had been noted in previous studies with IL- 
2. However, he said one of the mechanisms of action is that the 
cells will have their survival and activity enhanced by IL~2 
administration . 
Dr. Mahoney asked if it was possible that infusing TIL cells 
might introduce random tumor cells that escaped screening. Thus, 
the body would be seeded with single tumor cells which do not 
attract TILs and predispose the patient to development of 
multiple tumors? 
Dr. Rosenberg said this was one of the original problems they 
considered in thinking about the TIL protocols. However, a very 
stringent procedure was devised, and the FDA approved a set of 
criteria whereby any cells that are to be infused are carefully 
examined by a cytologist using melanoma-specific antibodies. If 
there is the trace of even a single tumor cell, then the cells 
are not administered. Further, in light of the extremely heavy 
burden of tumor cells in the patients who will receive the TILs, 
the number of any tumor cells that would escape detection would 
be at most on the order of 1/100,000 of the normal tumor burden. 
Dr. Mahoney questioned the occurrence of a cancer in a mouse that 
received retroviral supernatant intraperitoneally. Dr. Rosenberg 
said that Dr. Anderson had studied the tumor and that it did not 
contain any retrovirus. Since it was an old mouse which has a 3- 
5% incidence rate of spontaneous cancer, it was deemed not to 
have been as a result of the administration of the retroviral 
supernatant . 
Dr. Rosenberg said he wished to address Dr. Leventhal's questions 
as to the number of patients per dose level and how often 
measurements for toxicity would be taken. He said page 154 of 
the protocol contains a schedule of measurement of each of the 
toxicity determinants. He noted that each patient is his own 
control and therefore if any patient achieves intolerable 
toxicity, at any given dose, the escalation would be stopped. 
Dr. Leventhal said she did not see any form for annotation of 
this information. Dr. Rosenberg said that a toxicity form is 
filled out daily on all patients and that a nurse would enter the 
Recombinant DNA Research, Volume 14 
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