Recombinant DNA Advisory Committee- 9/12-13/94 
inflammation. 
Dr. H. Ginsberg said that vector dose should be expressed by the number of pfu rather 
than by the number of virus particles since infectivity of the virus differs from each 
preparation. 
Both adenovirus vectors used in this protocol and the previous CF protocols share the 
same viral backbone, and they have the same capacity to induce inflammation. It is not 
correct to assume that if the vector does not induce inflammation in monkeys, that it is 
safe for humans. Dr. Parkman added that the experiment was performed on naive 
monkeys not on immunized animals. 
Dr. H. Ginsberg said that if a vector induces a CTL response, it may increase 
inflammation upon repeat administration. 
Additional Comments 
Dr. Parkman explained that stereotaxic injection of vector will be performed in all the 
patients; and in some with resectable tumors, the tumor will be removed, while GCV 
treatment continues. This variation is different from the other retroviral brain tumor 
protocols. 
Dr. Samulski asked if the temperature-sensitive mutant developed in Dr. Wilson’s 
laboratory will decrease the chance of inflammation. Dr. H. Ginsberg said the mutant is 
leaky at body temperature, and it is inactivated only at 39° C. 
Dr. Parkman asked Dr. H. Ginsberg to clarify if E3 expression requires the presence of 
El. Dr. H. Ginsberg said El has an enhancer that affects E3 expression but it is not 
absolutely necessary for E3 expression. 
Investigator Response-Dr. Eck 
Dr. Eck conceded that Dr. Parkman’s concern about inflammatory response in a closed 
space within the skull is a valid one. For those patients who are to receive only the 
stereotaxic injection and no resection, careful screening of the degree of brain edema will 
be performed to determine their eligibility for the study. The patients will not be 
admitted if they have substantial edema, which decreases the expandable brain space. 
Dr. Parkman stated that a simple animal experiment will be able to address this toxicity 
question. Injecting the vector into the brains of 10 animals pre-immunized with the 
adenovirus would be helpful. Dr. Eck agreed that it is a technically feasible experiment; 
however, it will be difficult to predict brain swelling in human patients. 
Dr. Parkman said that this animal experiment can be easily performed on cotton rats, and 
if there is response, it will raise some concern. 
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