Dr. Neiman said he felt the Committee was trying to conduct the 
review in a fashion that sets the standards for future reviews, 
and this was not an attempt to delay important clinical research. 
He said the quantitative data presented showed considerable 
progress had been made, but the Subcommittee had deferred making 
a recommendation to the RAC pending submission of data to the 
Subcommittee. He said the issues central to the question of 
safety needed to be resolved. The data on retroviral 
replication, tumorigenesis , and undesirable effects on the 
recipient seemed to be limited by sensitivity of the assays as 
presented by Dr. Anderson. He said a more sensitive method would 
be to see if small numbers of viral particles could be amplified 
in a whole animal and cause viremia, and such data had still not 
been supplied. 
Dr. Anderson said Moloney murine retrovirus could not used in 
adult mice, but it has been done in newborn mice. Although there 
was considerable data, it was irrelevant. 
Dr. Neiman said he was not convinced there were no in vivo assays 
for amplification of small numbers of viral particles in an 
experimental animal comparable to humans, but progress was being 
made. However, he said, a meeting of the RAC was not the place 
where a final decision could be reached. 
Dr. Epstein asked if it could be determined that after TIL are 
put back into a patient and later removed from tumor, what 
fraction of the lymphocytes reisolated are in fact the marked 
population. Dr. Anderson replied this was a question now being 
asked and had not yet been determined. Dr. Epstein asked what 
protocol would be used to determine this. Dr. Rosenberg replied 
that the first question to be answered is whether the location of 
these transferred cells correlated with a clinical effect. The 
qualitative issue could be answered by stimulating all 
lymphocytes in a tissue subpopulation with lectin, growing them 
in IL-2, and looking under G418 selection to see if the marked 
cells were present. 
Dr. Rosenberg replied to Dr. Kelley’s assertion that the 
treatment had no potential benefit to the patient who is actually 
receiving the transferred cells. He said that this immediate 
procedure may not be therapeutic. However, if it were found that 
the transferred cells persisted in draining lymph nodes only in 
patients who respond, then the transduced cells from the lymph 
nodes could be isolated and their properties determined. He gave 
the example that if they were the only cells secreting tumor 
necrosis factor (TNF), then the gene coding for TNF could be used 
therapeutically in subsequent patients to produce therapeutically 
effective subpopulations of cells. Dr. Rosenberg stressed that 
delays in such experimentation would have deleterious effects on 
cancer treatment and he expressed a desire that the RAC vote at 
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Recombinant DNA Research, Volume 13 
