Recombinant DMA Advisory Committee - 2/4/91 
patients. 
Dr. Gellert said that one issue that still remained was the fact that third party payers 
may pay for the cost of direct treatment, but that they often refuse to pay for the cost of 
complications that result from experimental treatments, and he asked for Dr. Lotze's 
comments on this. Dr. Lotze said this was a problem outside the confines of a Federally 
supported institution such as the NIH, and that it was a societal issue that must be 
addressed. Even the NIH has a proviso in its informed consent to the effect that there is 
no guarantee that even the Federal government will make payment for injuries incurred 
as a result of experimental therapies. This was not his area of expertise, but he believed 
his protocol was reflective of the standard approach that is taken both inside the NIH 
and in academia, in dealing with the conduct of experimental therapies. 
Dr. Lotze wanted to make it clear that both a bacterial gene and a murine virus were 
being used in this protocol. He asked that he be allowed to forward a revised protocol 
to the RAC by the end of the week incorporating all the changes that had been 
discussed at the HGTS and here in this meeting. 
Dr. Post had two questions for Dr. Lotze. One question related to G418 selection. He 
asked whether this had been done before in TILs. His second question dealt with 
mention in the protocol of transduction of bone marrow cells. 
Dr. Lotze said that the reference to bone marrow cells was a word processing error 
which had crept into the protocol and had been removed from the current version of the 
protocol. However, the issue of G418 selection is deceptive in that sometimes cells that 
contain the gene will grow up in G418; other times these cells are less well protected 
from the effects of G418 and they do not grow. The intent of the protocol is to select in 
G418 to maximize the chance they would be able to detect the cells in the peripheral 
blood. A goal of the protocol would be to attempt to carry out parallel cultures. That 
is, TILs selected in G418 and TILs which were not selected. He would attempt to infuse 
cells that were cultured in G418 since they would be more likely to carry the marker 
gene and provide better information. However, because of G418's toxicity to 
mammalian cells, this may not be possible. Thus, the investigators would like to be able 
to give selected transduced cells but also have the possibility to give unselected suitably 
marked cells as well. 
Dr. Gellert was not clear on the issue of the Grade IV toxicity. He asked if it was really 
the intent to stop escalation only if 100% of the patients encountered Grade IV toxicity, 
and what would be expected to be seen at higher dose levels. 
Dr. Lotze said that the protocol defined Grade IV toxicity as "platelet counts that fall 
below 25,000 per cubic millimeter." This is a level of toxicity which precludes further 
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Recombinant DNA Research, Volume 14 
