July 30, 1990, Human Gene Therapy Subconmi ttee 
3. How could the patient distinguish between a biopsy performed for 
therapeutic reasons and one performed for research reasons? 
4, Could a patient decline to have a biopsy taken? 
Dr. Rosenberg said the consent form would allow multiple biopsies to be taken on any 
patient, and the number would vary from patient to patient. However, in most cases 
only local anesthesia would be required, the investigator would explain the purpose of 
each biopsy, and the patient would have the option of accepting or rejecting the 
procedure. A patient's declination of a biopsy would not affect his/her status in any way. 
Dr. Rosenberg said the protocol called for a maximum of five biopsies, one 
pre-treatment and four post-treatment. 
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 11^2 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. 
Recombinant DNA Research, Volume 14 
[199] 
