Recombinant DNA Advisory Committee - 03/1-2/93 
seriousness of the disease justifies this treatment; and that there is a reasonable 
expectation that this procedure will be therapeutic. Dr. Haselkorn inquired whether the 
risk of helper virus production could be quantitated. Dr. Miller said that although the 
probability of detecting helper virus in a production lot could be determined, there are 
mitigating factors in the human; such as complement which inactivate these viruses. 
Dr. Zallen noted that there was a discrepancy between the Iowa Methodist Medical 
Center and the University of Iowa Informed Consent documents regarding patients' 
financial obligations. The investigators should address the issue of patient liability in 
their response. 
Dr. Post asked the investigators to respond to the following questions: (1) What is an 
Ommaya reservoir and what is the history of its use? and (2) What is the status of the 
glioblastoma protocol which has already been approved by the RAC? Has an immune 
response to the NIH3T3 cells been observed? 
Presentation-Dr. Culver 
Dr. Walters called on Dr. Culver to respond to the questions and comments of the RAC 
members. Dr. Culver explained that one of the main principles of successful tumor 
therapy is to treat tumor cells that are entering into the proliferative phase. Glioma 
cells demonstrate a very heterogeneous rate of division; therefore, this therapy will be 
administered over a period of 60 days in order to optimize gene transfer into the greatest 
number of dividing tumor cells. Patients who have evidence of recurrent tumor following 
the initial therapy can be retreated through the Ommaya reservoir if that recurrence is 
on the margin of the resection. 
Dr. Culver said that the half-life of GCV is approximately 12 hours in humans. Data 
derived from rat and monkey animal models indicates that the producer cells survive for 
approximately 2 weeks. If the PA317 cells remain viable in humans for this period of 
time, the proposed treatment schema will allow for maximum gene transfer and provide 
the greatest opportunity for the bystander effect to occur. 
Dr. Culver stated that the description of the third injection of VPC into the Ommaya 
reservoir had been inadvertently omitted from the informed consent document; the third 
injection will be included in a revised version. He said that Dr. Gerard McGarrity of 
Genetic Therapy, Inc. (GTI), the vector supplier, would respond to the committees 
questions regarding safety testing of the VPC. 
Dr. Culver provided a brief update on the Oldfield glioblastoma protocol. To date, 5 
patients with surgically inaccessible brain tumors have received a single injection of VPC 
into various locations at the site of their tumor: 1 patient is currently receiving GCV 
Recombinant DNA Research, Volume 17 
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