Human Gene Therapy Subcommittee - 4/5/91 
were problematic, he volunteered to make any recommended changes so that the 
protocol could continue forward. 
Dr. Parkman said that perhaps the consent form was trying to be too all encompassing in 
its form, and it would be better to pull out just the sections dealing with IL-2, IL-4, and 
TILs, and have addendums to give to individual patients depending on their course of 
therapy. Dr. Lotze said that in all cases, the patients would have to agree to having the 
tumor removed, to having TILs grown up, and to receiving IL-2 and IL-4. In many cases, 
complications occur in growing up the TILs, and this possible eventuality requires a 
consent document that would explain other treatment options available to the patients. 
Dr. Kelley said that the TIL homing question continues to be an important question to 
answer. He asked Dr. Lotze how the data from muscle and skin would be handled, 
pointing out that the number of lymphocytes per gram tissue differs with tissue type. Dr. 
Lotze said he could quantify the T cells using PCR on T cell receptors or CDS. Dr. 
Kelley suggested they look at the percentage of total lymphocytes that are marked in one 
tissue versus another tissue. Dr. Lotze replied that there are two approaches that could 
be employed. One is to digest the tissue and count the lymphocytes, and the other 
would be to perform PCR on the T cell receptor, and use it as an internal standard for 
the total number of lymphocytes. Dr. Kelley asked if one would do the PCR on RNA or 
rearranged T cell receptor genes, as all cell types have unrearranged T cell receptor 
genes. Dr. Lotze answered that they could look for rearranged receptor genes but that 
Dr. Kelley had raised a good point. 
Mr. Capron asked if the study is likely to yield information about the effectiveness and 
possible risks of gene transfer to patients. Dr. Anderson said every gene transfer patient 
will be followed for life and will, therefore^ contribute to the total safety base. 
Dr. Lotze pointed out that cells in vitro grow in IL-2 and IL-4 better than in IL-2 alone, 
and that he would like to determine if the same is true in vivo, 
Ms. Meyers asked if the only difference between this protocol and Dr. Rosenberg's 
protocol is the addition of IL-4. Dr. Lotze indicated that there were two differences, the 
addition of IL-4 and the increased number of biopsies. 
Dr. Parkman said that this protocol includes crucial controls needed to assess TIL 
trafficking, and that the Rosenberg protocol has not answered this basic biological 
question. Dr. Parkman explained that the basis for using TIL is that the cells selectively 
return to the tumor and ultimately kill it. This had been the original hypothesis of the 
Rosenberg protocol, but such selectivity remains to be demonstrated. 
Dr. Gellert asked if the proposed IL-2/IL-4 treatment regimen is appropriate for 
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