proposals. He asked Dr. Rosenberg about the likelihood of giving 
infectious virus at the time of infusion considering the 3T3 
amplification could not be used because this test requires three 
weeks of cell culture. What tests would be used to define a "go- 
no go" decision on giving marked cells? He also inquired about 
any existing dose-response data on numbers of TIL cells required 
to exert a cytotoxic effect. He was told that the culture period 
could be extended until the desired number of cells had been grown, 
rather than harvesting and reinfusing on a predetermined date. 
Written comments from Drs. Mulligan, Varmus , and Temin were read 
into the record and Dr. Anderson stated that he would address these 
questions in his presentation. Dr. Kelley was unable to attend but 
called Dr. Walters to provide verbal comments for the record. In 
brief. Dr. Kelley was supportive of the proposal but thought that 
an animal model must be presented prior to the insertion of a 
therapeutic gene in place of the diagnostic marker gene. The 
investigators agreed with this plan. 
Dr. Parkman brought up the issue of the effect of the marking 
procedure on TIL trafficking patterns leading to a discrepancy 
between the behavior of marked vs. unmarked cells. On the same 
point. Dr. Singer noted the data concerning T-cell receptor 
rearrangements. She said that the incidence of clonal selection 
can be monitored. If there is no selection as a result of the 
marking proced. a, then there is no problem because the marked 
cells will be r presentative of the unmarked cells. In addition, 
animal studies will not be useful because trafficking in the mouse 
is not relevant to the human, thus providing a stronger rationale 
for proceeding with human studies. 
Mr. Capron called attention to a comment submitted by Dr. Varmus. 
Dr. Parkman explained that Dr. Varmus was suggesting that the 
investigators look for incorporation of the NeoR gene, but not its 
expression. Mr. Capron remarked that if the experiment is not 
going to produce the desired information, should this question be 
posed to an Institutional Review Board (IRB), or to the HGTS? 
Dr. Anderson 
Noting his previous appearances before the Subcommittee, 
Dr. Anderson apologized for not having presented certain 
information earlier and expressed his appreciation for their 
efforts. He noted that based on discussions he has had with 
members of the Subcommittee since the last meeting, there seems to 
be general satisfaction with the information he has provided. 
In a December 8 meeting with Food and Drug Administration staff, 
Dr. Anderson described levels of sensitivity of the assays used to 
detect replication competent virus against a large background of 
impaired virus. He has determined that it is possible to detect 
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