Recombinant DMA Advisory Committee - 3/3-4/94 
cover any costs related to research. 
Other Comments 
Dr. Parkman explained that the 10 to 12% transduction rate noted by the investigators 
refers to experiments conducted with cell lines rather than primary cultures; therefore, 
these results probably do not translate to the clinical setting. The investigators must 
address whether transduction affects the cytolytic activity of T lymphocytes. Tumor- 
specific trafficking of neo*^ marked T cells should be compared to surrounding normal 
tissue that has a blood supply comparable to the tumor. The marker gene may persist 
longer in blood cells than in tumor cells. 
Dr. Post stated that the protocol is very confusing and asked the investigators to provide 
a clear description of all clinical and experimental procedures. 
Dr. Zallen agreed with Dr. Secundy's assessment that the Informed Consent document is 
written in language that is not understandable to laypersons. Dr. Zallen stated that the 
section explaining that patients will be responsible for some of the research costs is 
unacceptable. The investigators should provide a detailed description of the informed 
consent process. 
Investigator Response--Dr. Freedman 
As a point of clarification. Dr. Freedman stated that two separate protocols and 
Informed Consent documents were submitted, one for the ongoing TIL protocol and the 
other for the gene marking study. No patient will be entered onto the gene marking 
study unless he/she has previously been entered onto the TIL study. The objective of 
the gene marking study is to determine whether neo*^ marked TIL can be detected at the 
tumor site 3 months following TIL administration. Three months after infusion of TIL 
cells, samples will be obtained by laparoscopy. A total of 10 patients will receive neo*^ 
marked TIL. Dr. Parkman noted the neo”^ gene was not detectable in melanoma 
patients 3 months post-infusion in Dr. Rosenberg's RAC-approved protocol. Dr. 
Parkman expressed his concern about the proposed experimental design. The 
investigators propose a single 90 day time point to detect neo*^ marked TIL. Dr. 
Freedman responded that this 3 month period is dictated by the ongoing TIL protocol 
because this time point is the optimal time period to examine the therapeutic effects of 
TIL Patients should not be required to undergo an additional laparoscopy in order to 
obtain tissue samples. This study would be very difficult to redesign. Dr. Smith inquired 
about the number of patients that will be evaluable at 3 months. Dr. Freedman 
answered that approximately 75% of the patients should be evaluable. 
Dr. Parkman expressed his concern that there is no study indicating that the marked TIL 
cells are detectable 90 days post-infusion. There may be no useful information to be 
obtained by examining the TIL cells at a single time point in the present study design. 
Dr. Parkman said that a shorter time point such as 30 days appears to be preferable. 
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Recombinant DNA Research, Volume 19 
