Recombinant DNA Advisory Committee - 06/1-2/92 
clonogenicity of the tumor cells is reduced. Dr. Culver stated that clonogenic assays had 
not been performed. 
Dr. Culver presented a final experiment regarding the bystander effect. He used a rat 
mammary cell cancer line. In contrast to the results obtained with the other cell lines, 
no bystander effect was observed. This particular cell line does not form monolayers like 
the other cells; suggesting that the bystander effect requires cell-to-cell contact. This 
phenomenon may be specific to adherent cells and may explain the results observed by 
other investigators such as Dr. Greenberg in Seattle, Washington, who are using cells 
grown in suspension. 
Dr. Blaese noted that he has performed trypan blue exclusion experiments in addition to 
thymidine incorporation assays and observed the same bystander killing effects on 
neighboring cells. 
Dr. Leventhal asked what would be the effect of injecting NIH 3T3 cells, which are on 
the brink of being transformed, into the human brain? If the patients are cured, will a 
different tumor occur in the same place where the NIH 3T3 cells were administered? 
What are the delayed effects? Dr. Culver stated that the monkey data suggests that 
there is no long-term survival of these cells. 
Dr. D. Miller referred to the Institutional Biosafety Committee approval of this protocol. 
This protocol was approved at Biosafety Level (BL) 2. Does this mean that patients 
must be confined to a BL2 level of containment? Dr. Wivel clarified that BL2 
containment was recommended for the manipulation of the virus and the vectors as 
opposed to the patients. 
Mr. Capron inquired if the surgically accessible patients would be treated prior to the 
surgically inaccessible patients; and if tumor transduction is unsuccessful, will the 
treatment be discontinued? Dr. Oldfield responded that the investigator has the choice 
as to whether surgically accessible or inaccessible patients will be treated. 
Dr. Murray asked Dr. Oldfield to respond to concerns raised by the committee members 
regarding the risks associated with stereotaxic injection in the surgically accessible 
patients. Dr. Oldfield stated that the only substantial risk is related to the tumor mass 
already present in the patient's brain. Patients must be screened carefully and chosen so 
that the mass of tumor is small enough to accommodate the additional volume of the 
murine cells. Patient selection is a critical criterion. Dr. Oldfield stated that the first 
patients that will be selected for treatment in this protocol will probably have right 
frontal or right temporal lesions that are relatively small. 
Committee Motion 
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Recombinant DNA Research, Volume 15 
