July 30, 1990, Human Gene Therapy Subcommittee 
Dr. Mclvor said that he had no doubt that, if a high enough level of TNF could be 
attained at the site of the tumor, the procedure could have a beneficial effect in tumor 
regression. However, he said it was unclear that such a level could be obtained in 
humans. Dr. Rosenberg said the NCI IRB extensively reviewed this issue and did 
approve the protocol. 
Ms. Meyers said that, if this were a protocol aimed at acquired immunodeficiency 
syndrome (AIDS), the room would be filled with patients demanding that the protocol 
be approved. Further, since the patients who will be entering the protocol are terminal 
cancer patients, she felt the risks involved were worth the possible benefits, and they 
should be given a chance to undergo this therapy. 
Dr. R. Murray asked Dr. Rosenberg to elaborate on the conditional approval from the 
NHLBI IRB which is contingent on primate toxicity studies that are underway. Dr. 
Rosenberg said that this protocol was approved by all local committees contingent upon 
HGTS and RAC approval. He said the primate toxicity data is now available and with 
HGTS and RAC approval they will return to the local IRBs and IBC for final approval 
before proceeding with the protocol. Dr. Murray said he understood that the protocol 
had been approved at the local level. Dr. Rosenberg said this protocol was no different 
from other protocols which the HGTS and RAC had approved, in which local approval 
was contingent upon HGTS and RAC approval of the protocol. 
Dr. Parkman said he felt the one contingency of HGTS/RAC approval was what was 
anticipated, but the fact is that there is a list of contingencies contained in the approval 
by the local committees. He felt the HGTS needed to consider whether they should 
accept a conditional approval from an IRB or IBC that contains any conditions other 
than HGTS/RAC approval. Dr. Mahoney suggested that the subcommittee determine 
whether the three contingencies of the IRB and IBC had been met and that a vote be 
taken on the protocol. 
Dr. Leventhal said she felt there were enough data on toxicity in humans and that 
waiting for data from two or three more monkeys was pointless when data already 
existed on TNF toxicity in 86 human beings. Dr. R. Murray said that the "Points to 
Consider" asks for preclinical animal data as a criterion for approval of a human gene 
therapy protocol. He said that the subcommittee was deviating from those guidelines if 
it approved a protocol when there were outstanding concerns over issues of safety. He 
said if there were no concerns as to safety, then the subcommittee could consider the 
protocol for approval. 
Dr. Epstein made the following motion: 
"I move that we approve this protocol contingent upon final approval by 
the all institutional committees and contingent upon changes in the consent 
[ 200 ] 
Recombinant DNA Research, Volume 14 
