Recombinant DNA Advisory Committee - 06/7-S/93 
from the research hypothesis. 
Review--Dr. Secundy 
Dr. Secundy stated that the investigators had adequately responded to her concerns 
regarding the time frame. However, questions about the exclusion and inclusion criteria 
remain. 
Other Comments 
Dr. Parkman stressed that the risks associated with the administration of gene marked 
cells, which will have no therapeutic effect, should be weighed against the importance of 
the data that will be obtained. Dr. Geiduschek stated the critical criterion for approval 
of this protocol is the consensus that this study will yield knowledge that will benefit the 
treatment of future patients. Dr. Chase has indicated that this protocol will not yield 
scientifically beneficial information as it is currently constructed. Therefore, Dr. 
Geiduschek stated that he is inclined to defer approval of the proposal. Dr. Parkman 
asked the PI to elaborate on how selectivity will be demonstrated, i.e., what are the 
methods that will be employed to demonstrate preferential trafficking of TIL to tumor 
versus adjacent normal tissues? Dr. Carmen said that the gene transfer procedure is not 
adequately described in the Informed Consent document in language that will be easily 
understood by lay persons. 
Investigator Response-Dr. Freedman 
Dr. Freedman stated that this protocol is an extension of an ongoing study of adoptive 
immunotherapy for the treatment of ovarian cancer. TIL will be marked with the neo R 
gene to determine the trafficking pattern of transduced cells. Ovarian cancer primarily 
involves the peritoneal surface and serosa. The objective of this study is to determine 
whether TIL preferentially localize to tumors. Marked TIL will be monitored by 
quantitative PCR. He presented preliminary tissue culture data. 
Dr. Parkman asked about the percentage of TIL that are transduced in vitro. Dr. 
Freedman responded that technical difficulties have been encountered in transducing 
CD8(+) cells, and no definitive result has been obtained. Dr. Miller commented that if 
transduction frequency is low, marked TIL will be difficult to track in tumor and 
surrounding normal tissues. Dr. Parkman said that if the sensitivity of detecting marked 
cells by PCR is unknown, the selectivity of TIL trafficking to tumor cites cannot be 
determined. Dr. Freedman responded that TIL will be administered intraperitoneally 
close to the tumor sites; therefore, a large fraction of TIL should localize to tumor. Dr. 
Freedman said that Dr. Deisseroth's laboratory will perform the PCR analysis. Dr. 
Deisseroth presented PCR data. Dr. Miller stressed the technical difficulty of 
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