Recombinant DNA Advisory Committee - 09/14-15/92 
form an oncogenic virus is critical. The investigators can perform assays that would 
determine the oncogenic potential of these vectors. If no transformation is observed 
using 10 8 particles, the vector is relatively safe. The p53 vector contains the p-actin 
promoter in reverse orientation that drives p53. He questioned if p53 could acquire 
mutations that make it an oncogene, and what would be the frequency of such an event. 
Regarding the bystander effect, Dr. D. Miller stated that the data demonstrates that 
there is a bystander effect capable of reverting cancer cells to normal morphology is not 
compelling. Data suggests that there is growth with all of the mixtures of cell types at 
seven days. The data would be more convincing if these cultures were extended over a 
longer period of time. 
Review-Dr. Hirano 
Dr. Hirano stated that she had two major concerns with this protocol. Patients will have 
their lung tumor cells transduced by the direct in vivo injection of retroviral vectors into 
the tumors. Preliminary data suggests that a transduction efficiency of 50 to 70% will be 
necessary to obtain an antitumor effect. The protocol specifies that this level of 
transduction will be accomplished by direct injection of 10 6 CFUs into the patient daily 
for five consecutive days. The treatment will be repeated monthly provided there is no 
evidence of disease progression. Since this vector will be injected directly into a patient 
for the first time, the RAC should determine whether the preclinical data addresses the 
issues of toxic or adverse side effects. 
The investigators used the LNSX vector for the preliminary experiments, but their 
packaging cell line was different from the one that they are proposing to use, PA317. 
Have any experiments been performed to demonstrate that high titer vector can be 
produced from PA317? Who will produce the vector supernatants? 
There is in vitro data with the antisense K-ras which suggests that the transduction 
efficiency can be increased as a function of the number of cycles of transduction. Is 
there analogous data for the p53 vector? In the investigator's response it was stated that 
PCR will be used to determine transduction efficiencies in vivo. Is there transduction 
efficiency data in the murine model where animals have been injected with the human 
cell line, HL60, and subsequently challenged with vector supernatant? 
Review-Mr. Capron 
Mr. Capron asked if there will be some degree of risk imposed on other persons exposed 
to the patient, i.e., hospital personnel and family members. The investigators indicate 
that there will be a 48-hour period that the patient may be capable of shedding virus. 
Are the precautions that will be taken adequate and is there a possibility that this virus 
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