Recombinant DNA Advisory Committee - 7/31/90 
3. A review of further data from the N2-TIL trafficking 
experiments, including available autopsy data. 
Dr. Clewell said these were addressed in an addendum to the 
protocol dated May 24, 1990. Dr. Rosenberg addressed all of 
these points, as well as other points relating to toxicity, at 
the meeting of the HGTS which took place on July 30. The main 
issues were: 
1. That the investigators relied on estimates of TNF 
expression based on production by TIL.pj^p. in vitro, and 
that levels of expression may differ via cellular 
expression in vivo; and 
2. That while transduced TILs are dependent on the 
addition of IL-2 in culture, this level of dependence 
is not clear in vivo, and therefore may be important in 
considering IL-2 withdrawal as a means of reversing TNF 
toxicity. 
Dr. Clewell said that, despite the drawback of not having a good 
animal model, he supported the proposal with some enthusiasm. 
The information to be gained from the studies seemed to justify 
the possible risks in light of the clinical status of the 
patients in whom the studies would be conducted. 
Dr. Epstein said he wanted to return to the issue of the consent 
form since he had made the motion at the HGTS meeting and that 
one of the contingencies to the motion was that the consent form 
be revised. 
Dr. Epstein said there was a lengthy semantic discussion of what 
constituted a Phase I trial. Since a Phase I trial is to 
determine toxicity and maximum tolerated doses independent of 
efficacy, efficacy was not an issue in the approval of the 
protocol. However, in the discussion by the HGTS, it was pointed 
out that the consent form was not proper for a Phase I trial and 
that Dr. McCarthy had made an impassioned request that the form 
be revised appropriately. Dr. Epstein said that, despite 
attempts at revision overnight by the investigators, the form 
still was not appropriate to a Phase I study. 
Dr. Epstein said the title of the study is "Gene Therapy of 
Patients with Advanced Cancer Using Tumor Infiltrating 
Lymphocytes Transduced with the Gene Coding for Tumor Necrosis 
Factor." Nowhere in the title does it reflect that it is a Phase 
I toxicity study. He said a better title would be, 
"Ascertainment of the Maximum Dose of Tumor Infiltrating 
Lymphocytes Transduced with the Gene Coding for Tumor Necrosis 
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Recombinant DNA Research, Volume 14 
