July 30, 1990, Human Gene Therapy Subconmittee 
given level, whereas "Appendix A" states that "First patient series equal to 
or five." Therefore, it is not clear how many patients are to be treated at 
each level before escalation, and how many events are required before 
cessation of escalation; and 
7. That something should be placed in the protocol that tells how toxicity will 
be stopped if it is felt to be intolerable. 
Dr. Leventhal said she also had some comments on the consent form, partly in response 
to Mr. Capron's letter, which had been received over the lunch hour. She said the 
sentence at the end of the first paragraph in the consent form says that chemotherapy 
may be an option, whereas it was previously stated that chemotherapy would probably 
not work in the patient's case. Dr. Leventhal suggested adding a section called 
"Alternatives," in which such issues could be addressed. She suggested the following 
wording: 
"You don't have to participate in this study if you don't want to do so. You 
can go to another physician for therapy at any time. There is no known 
curative therapy for your disease at the present time, and you could choose 
to have no further therapy." 
Dr. Mahoney said he felt the sentence in the consent form which states, "If you will 
participate in this part of the study, we will transform your lymphocytes," is misleading in 
that the entire protocol is a "gene therapy protocol." It should be reworded to omit the 
phrase "If you will participate in this part of the study..." 
Further Dr. Mahoney said he was not clear on what was known about in vitro control of 
cytokine secretion or expression by growth factors. Dr. Rosenberg said that this question 
had been studied extensively in patients receiving IL-2, alpha-interferon and TNF, and 
that in fact some cytokines can lead to secretion of others. 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 
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Recombinant DNA Research, Volume 14 
