Human Gene Therapy Subcommittee - 11/21-22/91 
suggested that the word be eliminated. The statement "as a result of being exposed to 
these transfer genes, it may be necessary to avoid intimate contact with others" is vague. 
If there is substantial concern about the transfer of genes through sexual contact, this 
concern should be more clearly stated. If the concerns are not warranted, then the 
statement should be eliminated from the informed consent document. The submission of 
this protocol is premature. 
Other Comments 
Dr. Parkman noted that the Points to Consider document requires that the investigator 
provide data regarding the percentage of cells expressing DNA. How much IL-2 does a 
transduced fibroblast produce on a per cell basis compared to T cells with some other 
stimulus? Is the amount of IL-2 expressed by transduced tumor cells equivalent to the 
amount expressed by transduced fibroblasts? Dr. Parkman suggested an in vivo 
reconstruction experiment in which the investigators inject enough transduced fibroblasts 
to express the same level of IL-2 expressed by transduced tumor cells. 
Dr. Mclvor added that another important experiment that should be performed would be 
to remove lymphocytes from the animal and demonstrate that they possess cytolytic 
activity against the target tumor. The proposed ratio of fibroblasts to tumor cells is very 
high. The total number of cells necessary for injection into animals to observe an 
efficacious response may not be available. The investigators did not provide any vector 
safety data, i.e., the presence of infectious agents or replication-competent helper virus. 
These data need to be provided. 
Dr. Parkman noted that the investigators propose to administer a total number of 
fibroblasts that is equivalent to measurable units of IL-2. The ELISA assays should be 
performed to determine optimum times for supernatant collection. The amount of IL-2 
produced may be a function of the period of time over which the supernatant is 
collected, not the number of fibroblasts. 
Dr. Epstein stated that the protocol has received three negative evaluations by the 
primary reviewers and questioned if the HGTS should continue discussion of the 
protocol. Drs. Royston and Sobol responded that they had additional information and 
requested that the HGTS allow them to present these data. Dr. Neiman agreed that the 
investigators should be provided the opportunity to respond and present additional data. 
Dr. Gellert noted that the standard set by the HGTS has been that investigators should 
provide critical data prior to the meeting, so that it can be carefully reviewed. Dr. 
Gellert added that even if significant data are presented today, the conclusions of the 
HGTS will probably not change. Dr. Miller polled the subcommittee members as to 
whether the investigator's written responses sufficiently answered any of the concerns 
that have been addressed by the reviewers. Dr. Parkman stated that no new data had 
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