Human Gene Therapy Subcommittee - 7/30/90 
Dr. McCarthy said that the informed consent document alludes to 
possible therapeutic benefits. In light of the discussion over 
the purpose of the study (Phase I versus Phase II) , he felt it 
would be unfair to allow the patient to place false hopes in this 
kind of study. Dr. Epstein said the ambiguity is stated on the 
second page of the protocol. It states that the objective of the 
study is, "to evaluate the toxicity and possible therapeutic 
efficacy of administration of TILs." 
Dr. Rosenberg clarified by noting that the informed consent 
document clearly states, "Because these treatments are 
experimental, it is not possible to determine if you'll receive 
any direct benefit from them. The purpose of the study is to 
determine the maximum doses of a treatment consisting of your own 
gene-modified immune lymphocytes and IL-2 that can be 
administered." He said the protocol had been carefully selected 
because there is a belief, based on experimental evidence, that 
the treatment may provide therapeutic benefit to patients as they 
reach the highest tolerated maximum dose. 
Dr. Epstein asked whether the Phase II protocol, if undertaken, 
would start at the highest tolerable dose. Dr. Rosenberg 
explained that the plan would be to begin at a dosage which was 
maximally tolerated by 80 percent of patients in the Phase I 
study. He noted that the investigators would come back to the 
HGTS and the RAC before beginning a Phase II study, despite the 
fact that there would be essentially no change in the protocol. 
Dr. Parkman asked why the tumors continued to grow in the murine 
model for a period of up to 12 days before systemic 
administration of TNF showed the quick resolution of the cancers. 
Dr. Rosenberg said that it appeared that systemic TNF 
administration produced no antitumor effects in the mice until 
the tumors reached a size of 3-5 millimeters in diameter. He 
said he believed that TNF worked on the vasculature of the tumor 
itself and that the tumor must develop a responsive vasculature 
before the TNF can work. 
Dr. Mclvor said that he had no doubt that, if a high enough level 
of TNF could be attained at the site of the tumor, the procedure 
could have a beneficial effect in tumor regression. However, he 
said it was unclear that such a level could be obtained in 
humans. Dr. Rosenberg said the NCI IRB extensively reviewed this 
issue and did approve the protocol. 
Ms. Meyers said that, if this were a protocol aimed at acquired 
immunodeficiency syndrome (AIDS) , the room would be filled with 
patients demanding that the protocol be approved. Further, since 
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