Recombinant DNA Advisory Committee - 06/1-2/92 
Presentation— Dr. Oldfield 
Dr. Murray called on Dr. Oldfield to respond to the questions and comments of the 
primary and secondary reviewers as well as the other committee members. Dr. Oldfield 
explained that the tumors being proposed for treatment in this protocol are ideal targets 
for consideration by this localized treatment strategy. Unlike other malignancies, 
patients with primary CNS tumors die of local growth, not disseminated disease. 
Dr. Oldfield responded to Dr. Zallen's question regarding the scientific advantage of 
performing stereotaxic surgery prior to surgical resection of the tumor. By injecting the 
vector producing murine cells stereotaxically into the brains of these patients seven days 
prior to resection, information will be obtained regarding the survivability of these cells 
and whether or not the tumor cells are being transduced in the presence of these murine 
cells. 
Dr. Oldfield stated that patients with metastases are being included as a treatment group 
for this protocol since metastatic brain tumors are very well defined tumors, and they do 
not infiltrate the contiguous brain for distances more than a few cell layers. These 
metastases may be more sensitive to this treatment than the primary tumors. 
Dr. Oldfield said that the investigators were working in cooperation with Genetic 
Therapy, Inc. (GTI) which will be supplying the vectors for this protocol. 
Dr. McGarrity responded to Dr. D. Miller's question regarding the glycoprotein 
component. Dr. McGarrity reiterated Dr. Oldfield's response that GTI is currently in 
the process of constructing a second generation vector that does not contain the herpes 
simplex virus glycoprotein-H coding region, which is of concern to the RAC. However, 
in light of the fact that all of the experimental data for this protocol has been generated 
using the original vector, it is reasonable that the investigators should go forward with 
their original proposal. Dr. McGarrity said that if efficacy and safety data for the 
improved vector demonstrate that it is superior to the original vector, the investigators 
will submit a request to use the improved vector in the form of a minor modification to 
the protocol. Dr. McGarrity noted that the investigators will be using the original PA317 
packaging cell line which was described in the protocol, not the PAT 2.4. 
Dr. D. Miller asked Dr. McGarrity to explain the differences between the two packaging 
cell lines. Dr. McGarrity stated that there is no functional difference between the two 
packaging cell lines. The only difference is that the PA317 cell line contains the TK 
marker gene. Therefore, the animal toxicity data generated using the PAT 2.4 packaging 
line should be representative of the PA317 cell line. 
Dr. Oldfield responded to Dr. Hirano's question regarding the timing of administration 
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Recombinant DNA Research, Volume 15 
