Recombinant DNA Advisory Committee - 21^191 
Dr. Lotze said that this research represents a costly investment to the institutions 
embarking on it. The estimated cost of merely growing up cells for adoptive transfer is 
in the range of $20,000 to $30,000 dollars per patient. Dr. Lotze said his comments 
should be taken in light of these factors. 
He said that the original protocol submitted to the RAC called for administration of 11^2 
with TlLs and that in the time that had elapsed between the original submission and 
today, the protocol had undergone several iterations in an attempt to improve on the 
therapy. The introduction of IL-4 into the protocol was one attempt to enhance the 
growth of TILs and is something which has been shown to increase growth and activity of 
TILs. Approximately 20-30 patients had received TILs grown in combinations of IL-2 
and IL-4 and that there were no differences in terms of responsiveness. He identified 
one patient who had received transduced TILs, a portion of which were grown in 
combinations of IL-2 and IL-4. 
Dr. Lotze said there were two approaches to improving this therapy: 
1. The introduction of cytokines, such as TNF, which can improve the efficacy 
of the cells; and, 
2. Methods to improve the ability of the cells grown in tissue culture to be 
able to home to tumor sites more efficiently and perhaps engraft and 
persist for longer periods of time. 
Dr. Lotze said his protocol was seeking to use the first approach, to use cytokines which 
are believed to be important for improved T cell growth and activity. 
He said there was substantial information gained from treating over 100 patients at the 
National Cancer Institute (NCI) with IL-4 alone, or IL-2 plus IL-4. In fact, the major 
goal of this protocol is to obtain tumor specimens repeatedly in an attempt to assess 
whether TILs have targeted to the sites in ways that have been anticipated. 
Dr. Lotze said it had become apparent that there are toxic effects associated with this 
type of therapy. Because of the terminal nature of the patients who will be entered into 
the protocol, and the fact that they have failed all other known therapies, the risk to the 
patients is minimal. 
In responding to questions as to the actual dosage of cells to be used, Dr. Lotze admitted 
that the protocol was somewhat confusing. He explained that they would take 
approximately half of the TILs initially, attempt to transduce them, and insert the 
neomycin phosphotransferase (NPT) gene. The goal is then to give no more than 10% 
of the transduced TILs along with non-transduced TILs. He had assayed TILs into 
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Recombinant DNA Research, Volume 14 
