Recombinant DNA Advisory Committee- 9/12-13/94 
to be successful, it would be important to ascertain which one has the least side effects 
against normal tissues. 
The investigators have a significant amount of preclinical data in animals showing that: 
(1) the injection of both rat and human tumors in vivo results in decreased tumor growth 
or in some cases destruction of all the tumors, and (2) the injection of the adenovirus 
vector does not result in demonstrable clinical toxicity. 
The protocol has a lot of similarities to the Oldfield protocol. Two groups of patients will 
be studied, those who have resectable and non-resectable tumors. In both groups, the 
patients initially will have the adenovirus vector injected stereotactically and then will 
begin on systemic GCV treatment two days later. When patients have resectable tumors, 
the tumors will be resected 7 days later and local injections of the adenovirus vector will 
be given, and GCV continues for another 7 days. The removed tumor will be assayed for 
the presence of the adenovirus vector. The investigators will take advantage of the 
Positron Emission Tomography (PET) scanner available at their institution to measure the 
metabolic changes that occur in the transduced tumors. In an individual with multiple 
tumors, it will be possible to compare the metabolic effects of the injected tumor versus 
the non-injected control to determine if there is any distant bystander effect. 
The major concern raised by Dr. Parkman was the potential inflammatory response in the 
closed space of the central nervous system when the vector is stereotactically injected into 
the brain of individuals who are already immunized to the adenovirus. This response is a 
serious concern when swelling occurs in the closed space after stereotactic injection, but is 
less of a concern when a tumor is resected since expandable space will be created. The 
investigators have not addressed the clinical sequelae of this complication. 
Overall, most elements of the protocol have been previously approved by the RAC, i.e., 
general therapeutic approach, the adenovirus vector backbone, and the cDNA insert of 
HSV-TK gene. The vector was constructed by Dr. James Wilson’s laboratory for his RAC 
approved CF protocol. The only remaining question is the potential inflammatory 
response to the adenovirus vector in the closed space of the central nervous system. 
Review— Dr. Motulsky 
Since many of the aspects of the protocol have been mentioned by Dr. Parkman, Dr. 
Motulsky did not see that any other novel issues needed to be raised. He said that this 
protocol is very well written and could be approved as is. 
Review-Ms. Meyers 
Mr. Meyers commented that this protocol was another gene therapy for brain tumors and 
questioned if there was any need to conduct another of this kind of study. The 
investigators responded that this approach uses a different vector. Ms. Meyers asked the 
investigators to elaborate on this issue. Regarding the Informed Consent document, Ms. 
Meyers pointed out the barrier contraception was not mentioned for males; and she 
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