Human Gene Therapy Subcommittee - July 29-30, 1991 
patients with immune system failure will not be treated. Dr. Leventhal said a cell 
marker is not a quantitative estimate of tumor burden. Since a laparotomy is 
prohibited four weeks prior to treatment, tumor size may have increased by the time 
the treatment is administered. Dr. McCune stressed that this is a Phase I study to 
determine a safe dose of treatment and to assess any immunologic effects. It is asking 
too much in a Phase I study to judge fully the question of efficacy. 
Dr. Leventhal asked if the protocol will measure urine output, creatinine levels, and 
uric acid. The toxicity criteria should be designed in expectation of treatment success. 
Could the success of the treatment be a result of tumor lysis syndrome? Dr. McCune 
said the investigators will look for possible complications. 
Dr. Parkman said it is not clear how immune function will be determined following 
treatment. Antigen-specific skin tests should be done before and after treatment to 
assess reactivity changes. 
Dr. D. Miller asked if there should be particular concern about the fact that the PA-1 
line has been passaged over a long period of time. Has PA-1 been screened for 
Mycoplasmal Dr. Freeman replied this had not been done. 
Dr. Mclvor asked what assays will be used to check for replication-competent virus in 
the PA-1 cell line. Dr. Freeman said they had not tested for replication competent 
virus. 
Dr. Parkman said the similarity of the presenting cell type to the target tumor is 
irrelevant. There is no need to use an ovarian cell just because the target cell is an 
ovarian cancer cell. 
Dr. Mclvor said the ratio of administered cells to the number of pre-existing tumor 
cells and how that relates to the efficacy assays has not been answered. If the 
maximum number of tumor cells that will be administered to the patient is 3 X 10^®, 
what is the number of pre-existing tumor cells that might be anticipated in the patient, 
and how does that relate to the preclinical data that have been provided? Dr. 
Freeman said that in the Phase I study, the proposal is to determine the maximum, 
effective, and safe dose. Potentially, multiple injections can be done to treat the same 
patient. If there is a need to increase the dose beyond 3 X 10^°, an amendment to this 
protocol would have to be submitted to the RAC. 
Dr. Leventhal said the HGTS is trying to insure that the maximum amount of 
information is obtained from this Phase I study. This would include an estimation of 
the ratios of input cells to resident tumor cells in the patient. Tumor cell numbers can 
be evaluated in the patient by peritoneoscopy. Also, further ratio experiments in mice 
would be helpful. She asked the investigator to provide further data concerning TK+ 
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Recombinant DNA Research, Volume 14 
