Recombinant DNA Advisory Committee - 2/10-11/92 
tumor burden be determined in these patients? (3) Has tumor burden been assessed and 
what is the estimated tumor cell number? and (4) How many transduced cells are 
necessary to treat these patients, based on the animal studies? Dr. Freeman responded 
that the investigators would aim for a ratio of transduced cell to tumor cell of at least 1:1. 
Dr. Mclvor asked whether the patients' tumor burden would be determined. Dr. Freeman 
answered that all patients will undergo a laparotomy or laparoscopy, and imaging 
techniques will be used to determine the tumor burden. Dr. Mclvor assumed that the 
investigators will be estimating the tumor volume and using conversion factors to 
determine the cell number. Dr. McCune added that most of the patients have already had 
a laparoscopy or laparotomy, which is usually the mechanism by which their residual 
tumors were discovered. 
Dr. Krogstad asked how this treatment would affect extra-abdominal tumors. Dr. Freeman 
responded that animal model data suggests that treatment has effected extra-abdominal 
tumors; however, it is unclear to what extent. Any patient having tumor outside of the 
peritoneal cavity is ineligible for this study. 
Dr. Haselkom asked if a quantitative relationship between circulating CA-125 antigen and 
the number and growth rate of tumor cells could be determined. Dr. McCune answered 
that CA-125 levels cannot directly correlate with the number of tumor cells and these 
levels vary tremendously between patients. 
Dr. Post asked if there were any other animal studies that could be conducted to provide a 
foundation for the human studies. Dr. Freeman responded that the animal models could 
be improved; however, there is an abundant amount of knowledge that could be obtained 
from the human studies. The best combination would be to begin the human studies and 
continue to refine the animal experiments. 
Dr. Geiduschek asked with what certainty Dr. Freeman could ascertain that the patients 
are in relapse. Dr. Freeman stated that there are problems with any diagnostic system. 
For this protocol, patients must have evidence of macroscopic or microscopic disease. 
Dr. Mclvor stated that the experimental data shown in Figure 9 were most relevant to the 
human situation. The increase in survival is five days for this animal experiment. The 
RAC needs to contend with how to extrapolate these data to humans. Dr. Freeman 
admitted that this animal model may not be the most appropriate because the tumors are 
much larger than in the patient population. Dr. Mclvor agreed that this animal model was 
the closest model to humans, and the response in humans would probably be greater. Dr. 
McCune added that the investigators chose the most difficult setting. 
Dr. Geiduschek asked if the mice had been autopsied to determine the cause of death. 
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