Recombinant DMA Advisory Committee - 2/4/91 
which the NPT gene was inserted and there was no difference in terms of cytolytic 
activity. The question of how the cells would react in vivo is another matter and can 
only be answered by giving a pure population of such cells, which is not the intent of the 
protocol. In previous studies it has been possible to transduce upwards of 50% of the 
cells, but only 20% end up becoming marked with the NPT gene. 
Dr. Lotze said that the issues regarding tumorigenesis were difficult to resolve, but there 
had never been an identifiable tumor caused in subhuman primates using this identical 
vector, even when giving concentrated cultures of this virus intravenously. There were 
no instances of tumor production by the virus in murine models. This does not mean 
that it cannot occur and noted that it was still of concern to the investigators, even to the 
point of their evaluating the potential use of other vectors that can be very precisely 
inserted. The vector they were exploring was a adeno-associated virus vector which 
inserts on chromosome 19. The vector has not been available yet for study but is 
currently being evaluated. He underlined that the vector they are planning to use is the 
identical vector that has been used in patients previously and as yet there is no evidence 
of tumorigenesis in animals. 
Dr. McGarrity asked whether the cost estimate of $20,000-$30,000 for adoptive transfer 
was based on just working with the TILs and disregarded the marked gene. Dr. Lotze 
said that this is just the cost associated with the TILs and there is no cost charged for 
marking. None of the very experimental components of the therapy would be charged to 
the patient, including the gene marking. 
Dr. Krogstad asked what the patients would be billed for in these studies. Dr. Lotze said 
that his institution had a long history of involvement in testing novel therapies such as 
liver transplantation and that it had championed the use of biologic agents. Every 
attempt is made to obtain payment from third party payers prior to administration of 
therapy to patients. A large infrastructure has evolved to assist patients so that no 
umeasonable costs are borne by the patient. Such costs are handled on a case-by-case 
basis. 
Dr. Krogstad was concerned with the continuing struggles relative to payment by third 
party payers. He wondered whether this would not be such an impediment to human 
gene therapy that it may in fact bring into question whether it can be performed outside 
the confines of the NIH. Such circumstances could limit the transfer of this technology 
from experimental to applied research and into general practice. 
Dr. Lotze remarked that cautions were well founded but that he wanted to keep these 
issues separate from the direct issues surrounding approval of the protocol by the 
committee. He reiterated that no costs associated with the experimental therapy, 
including the administration of TILs and gene marking of TII^, would be borne by the 
Recombinant DNA Research, Volume 14 
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