Recombinant DNA Advisory Committee - 09/14-15/92 
the injection target would be lost. He asked Dr. Roth if he had any reservations about 
not resecting the entire lesion. Dr. Roth said that in actuality, the tumor will be resected 
as much as possible and noted that this standard surgical technique results in 100% 
recurrence. It is impossible to resect these tumors completely. Dr. H. Miller asked if 
the procedure will be one of irrigating the resected area rather than actual injection into 
the remaining tumor bed. Dr. Roth stated that the area would be irrigated. 
Dr. H. Miller asked about the stopping rule for progression of metastatic disease. Dr. 
Roth responded that if local control of tumor is observer, and there is progression of 
metastatic disease, the patient will have to be removed from the protocol. 
Dr. D. Miller said that the vector used for the preclinical studies was prepared by co- 
cultivation with packaging cells, and an extremely high viral titer was obtained. The 
protocol stated that PA317 cells will be used; this differs from the preclinical 
experiments. If the new packaging line produces lower viral titers as the investigators 
have indicated, will the in vivo experiments be repeated using the new vector? Dr. Roth 
said that the efficacy of the new vector will be monitored to ensure that similar titers are 
obtained. Dr. D. Miller stated that GTI may not have experience with producing viral 
titers of 10 7 CFUs continuously. Dr. McGarrity stated that GTI consistently produced 
vectors which produce viral titers of 10 7 CFUs. Dr. D. Miller asked if the animal 
experiments will be repeated. Dr. Roth said that some of the animal experiments will be 
repeated once the packaging cell line is established; however, the in vitro experiments 
correlate very well with the animal model data. It is reasonable that only the in vitro 
experiments will have to be repeated with the new packaging cell line. 
Dr. D. Miller asked if normal cells express the same genes as the transduced cells, why 
don't normal cells secrete the bystander factor and suppress neighboring tumor cells? 
Dr. Roth said that cells lose their transformed phenotype but they are not normal, i.e., 
they do not flatten out. Many investigators are currently conducting experiments to 
biochemically characterize the factor that produces the bystander effect. It is not known 
what the actual transcriptional events are at this time. 
Dr. Dronamraju asked if any primate data exists. Dr. Roth said that it is not possible to 
develop this type of tumor model in primates or canines because of the complexities of 
having to identify the specific oncogenes involved and the necessity to use an 
immunosuppressed model if human tumor cells are used. 
Dr. Post asked if experiments have been performed on NSCLC cells that do not possess 
either the K-ras or p53 mutations. Dr. Roth said that they have performed these 
experiments on several cell lines, and no effect has been observed on growth. 
Dr. Parkman said that the investigators have fulfilled the requirement of providing the 
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