Human Gene Therapy Subcommittee - 11/21-22/91 
that in the animal studies, they have observed a response to fibrosarcomas, colon 
carcinomas, melanomas, and renal cell cancer. It would be preferable to open the study 
to all tumor types because it is difficult to predict exactly which patients will respond to 
this treatment. Dr. Royston encouraged suggestions from the HGTS members regarding 
the range of tumor types. The goal of this study will be to evaluate the toxicity 
associated with TLr2 secreting fibroblasts at the local site. Data derived from animal 
experiments suggest that fibrosarcomas, colon carcinomas, melanomas, and renal cell 
carcinomas are responsive to this form of therapy. Dr. Royston noted, however, that 
there is probably no direct relationship between the animal models and human cancer 
with regard to tumor types. 
Dr. Parkman stated that experiments should be performed using the tumor types that are 
historically most responsive to immunotherapy. Dr. Leventhal stated that the study 
should be designed to demonstrate that the transduced fibroblasts are expressing IL-2 
and whether an immune response has occurred as a result of the IL-2 secreting cells. 
1 Therapeutic efficacy is not expected to be demonstrated in these patients because of 
their enormous tumor burden; their immune systems may be paralyzed. Dr. Leventhal 
suggested that the investigators should determine which patients exhibit an immune 
response before limiting tumor types. Eligibility should be determined in terms of the 
experimental endpoints. In addition, patients should not have received extensive 
chemotherapy that would render them immunoincompetent. The most appropriate 
limitation on patient eligibility would be patients who have no curative conventional 
therapy available. These criterion would not limit the study to any particular tumor type. 
Dr. Leventhal stated that the investigators should avoid any experimental design in which 
they would not be able to interpret the results. If the treatment is not efficacious and 
the investigators have not determined that immune manipulation has been achieved, then 
one cannot determine if the negative results are the result of the wrong dose or 
I ineffective treatment. The doses of IL-2 secreting cells must be determined more 
precisely. Describing the dose in terms of IL-2 units alone is not sufficient. 
Dr. Leventhal inquired if steroids antagonize the effect of IL-2. Dr. Sobol stated that 
steroid administration may inhibit an inflammatory response and that the effect of 
steroids on this treatment should be examined. Dr. Leventhal suggested that the 
investigators consider the use of Motrin instead of steroids. She noted that IL-2 causes 
systemic toxicity and added that the investigators should state how they would treat such 
toxicity. 
Dr. Leventhal noted that the issue of gene transfer must be addressed by the 
investigators. A local biopsy should be performed after X number of days; the X may be 
of critical importance. In addition, the effect of the inserted gene must be demonstrated, 
e.g., measurement of serum IL-2 levels. Dr. Sobol said that standard assays exist for 
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