Recombinant DNA Advisory Committee - 06/1-2/92 
Dr. D. Miller described the proposed vector as a variation of the previously approved 
vector GIN. The proposed vector, GITkSvNa, contains the TK gene. He cautioned that 
the TK insert in this vector contains a portion of the herpes simplex virus glycoprotein H 
coding region with its promoter. Although there is a slight possibility that this protein 
may be antigenic in patients, he would approve the use of this vector. The investigators 
have informed the RAC that they have a new vector which eliminates the herpes simplex 
promoter; however, he suggested that the investigators use the original vector since this 
one was used for all in vivo and in vitro experiments. 
Review-Dr. Hirano 
Dr. Hirano said that the mode by which the vector is to be delivered to the target cells, 
human brain tumor cells, is unprecedented. The investigators propose to inject murine 
vector producing cell lines directly into the patient's brain. Initially, there were concerns 
regarding the potential toxicity and survivability of these cell lines. However, the 
investigators have submitted monkey toxicity data demonstrating that the producer cell 
lines survive up to 15 days, and that no obvious toxicides were observed. 
Dr. Hirano asked the investigators to explain why the PA317 producer cell line was 
chosen since the protocol specifically states that the PAT 2.4 producer cell line will be 
used. 
Dr. Hirano asked the investigators about the survivability of the TK-containing cells and 
whether or not PCR analysis had been performed on the sacrificed monkeys to detect 
the survivability of the producer cells. 
Dr. Hirano stated a concern with the patient informed consent document regarding the 
language used to describe the viral vector. The investigators refer to this vector as the 
car or the vehicle. This description should be expanded to state that the vector will be 
injected into the brain via another vehicle , i.e., mouse cells. 
Review~Mr. Capron 
Mr. Capron stated that the investigators had been very responsive to his questions and 
concerns. The informed consent document had been clarified significantly. In response 
to Dr. Hirano's comment regarding injection of the mouse cells, he noted that they had 
addressed this matter in the revised informed consent document. 
Mr. Capron suggested that perhaps it would be more appropriate for the investigators to 
describe this protocol as "the treatment of brain tumors by transduction with the TK gene in 
order to render them susceptible to ganciclovir" as opposed to "the gene therapy of brain 
tumors". This issue would be a relevant topic for discussion by the RAC. 
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Recombinant DNA Research, Volume 15 
