Human Gene Therapy Subcommittee - 4/5/91 
1. Further evidence is required that the investigators are able to carry out 
PCR with a sensitivity of detection of 1 marked cell out of 10^ cells; 
2. Further information is required on how the semi-quantitative PCR is to be 
done, whether by dilution of marked cells or by something more elaborate, 
and 
3. Further information is required on the controls to be used in the semi- 
quantitative PCR assays. 
Dr. Gellert said that in terms of clinical outcome additional clarification was also 
necessary in the following areas: 
1. What is the definition of a response and how will responses be measured, 
and 
2. How will improvements be determined? 
Dr. Gellert noted that the consent form had been improved; however, problems still 
existed in its wording. Questions he brought forth in his review were addressed 
adequately by the investigator in this new revised consent form. 
Dr. Parkman said the subcommittee should not focus its attention on the issues of IL-2 
and IL-4, or the responses to treatment, or the effect of TIL cells. He felt the real issue 
of importance was that of marking with the purpose of looking at cell trafficking. Since 
marked TIL cells are only scientifically relevant for their marking characteristic and offer 
no therapeutic benefit to the patient, one of the entrance criteria for the study should be 
that patients are willing to undergo multiple skin and muscle biopsies in addition to 
tumor biopsy in order for the study to be valid. 
Furthermore, Dr. Parkman wanted to hear more from Dr. Lotze about the latest version 
of the semi-quantitative PCR assay. An important question is whether the quantitation 
of normal tissue controls by PCR would be adequate to address questions of cell 
trafficking. The revised protocol is better, but issues of quantitation are crucial to 
obtaining an answer of whether this therapy provides any specificity. 
Dr. Lotze said that because of the time constraints on the meeting, he would not make 
his planned presentation, but merely address the specific concerns that were raised by 
Drs. Parkman and Gellert. 
Dr. Lotze said the most serious criticism of the protocol is that it may not be able to 
answer the questions it sets forth. This really amounted to a question of how well 
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