July 30, 1990, Human Gene Therapy Subcommittee 
vims? 
9. How many dry mns have been performed, and what is the Southern blot 
data on these? Is proviral stmcture and copy number maintained? Are 
these data available to review? 
10. What is the current status of marked TIL trafficking studies? Do they 
support homing at a level of .015% per gram? 
11. In human experiments, how will one determine what part of the efficacy 
can be attributed to TNF gene transfer and expression? 
12. How was the TNF level of 150 picograms per 10^ cells per day (minimum 
level of transduced TIL) calculated? 
Further, Dr. Mclvor made the following suggestions to the investigators: 
1. That there be an alternative assay for ecotropic and xenotropic vims; 
2. That an assay of transduced TIL supernatants and patients' sera for TNF 
(neo)vims be performed; and, 
3. That a small group of subcommittee members analyze the safety data. 
Dr. Mahoney said he reviewed the proposal and found that Dr. Mclvor had covered 
most of what he thought were the major issues. He did call the subcommittee's attention 
to the fact that this was a Phase I cancer therapy protocol and that the patients will be 
desperately ill with very short expected lifespans. He said that, because of this, it was 
important to closely review the safety issues. However, he did not believe prolonging 
experimental verification of possible efficacy was justified. He said the investigators had 
been asked to share information in three general areas: 
1. Ongoing toxicity studies in monkeys; 
2. Effectiveness of a neutralizing antibody in neutralizing TNF effects in a 
murine animal model; and, 
3. Trafficking data on how many TIL cells get to tumors and what kind of 
TIL cell aggregation is expected, so as to be able to judge what levels of 
TNF will be secreted. 
Dr. Mahoney said he was interested in organ-specific toxicity of TNF in the liver, spleen, 
and lining of the gut as a result of sequestration of TNF which does not reach the tumor. 
Recombinant DNA Research, Volume 14 
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