Human Gene Therapy Subcommittee - 11/21-22/91 
Dr. Miller asked to what extent the investigators were able to mark the vectors, and how 
much data existed on the markers. Dr. Economou said that over the last 18 months, no 
fewer than 30 different TIL populations had been transduced using a variety of vectors 
with transduction frequencies between 1 and 5% with LNL6. Transduction frequencies 
with GINa have been higher. The problem with cytokine vectors is with the expression 
and selection of pure cell populations in which there is integration; however, the 
transduction and success rates are very good. 
Dr. Miller asked how a determination could be made that a specific transducable cell 
population is isolated if nonselected cells are used. Dr. Economou said that a 
heterogenous population is used; however, there is probably a subpopulation of cells that 
is receptive to transfection. 
Dr. Miller stated that there are several possible implications. Since only a small 
proportion of cells are marked, the sensitivity is lower. If the marker is found at the 
tumor site, the question remains as to whether the total population or a subpopulation of 
cells traffic to the tumor site. This result would be difficult to interpret in terms of the 
original bulk population. 
Dr. Parkman said the unproven assumption was that transfection would be random. 
There could be a negative bias against transfecting certain subpopulations of cells. 
Transfection of these subpopulations of cells would require a 100% marking. 
Dr. Miller concluded that the patients were not being compromised and that valuable 
information could be obtained from the protocol but with many qualifications. Dr. 
Economou said the greatest potential was in obtaining data concerning the trafficking 
and therapeutic potential of TIL since little information is available about their mode of 
action. 
Ms. Meyers said the protocol should not be approved because there was no direct 
benefit to patients. Questions still remain concerning the vectors. Dr. Economou noted 
that direct benefit was achieved in the patients who had clinical responses in spite of 
their incurable disease. Ms. Meyers responded that this result occurred through TIL 
therapy without gene marking, so that the marking would expose patients to risk without 
certainty that new knowledge would be gained. 
Dr. B. Murray said that if the HGTS voted to conditionally approve the protocol, a short 
summary of the safety data should be provided to the RAC. Dr. Parkman disagreed with 
Ms. Meyers, stating that this protocol was an improvement over the TIL protocols that 
had previously been approved by the HGTS and the RAC. This protocol is designed to 
improve selectivity in the trafficking of TIL to tumor. Dr. Erickson agreed, noting that 
the change in vector was trivial. 
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