Recombinant DNA Advisory Committee - 12/3-4/92 
Review— Dr. DeLeon 
Dr. Murray called on Dr. DeLeon to present her primary review of the protocol 
submitted by Dr. James Wilson of the University of Michigan Medical Center, Ann 
Arbor, Michigan. Dr. DeLeon stated that the significance and biological basis for 
adenovirus-mediated gene therapy of CF and the natural history of the disease have 
been extensively presented by Drs. Parkman and Crystal. Therefore, this review will be 
limited to comments on the procedures proposed in Dr. Wilson's protocol. 
A total of 12 patients will be enrolled in this protocol. Patients will receive escalating 
doses of the vector, which will be administered by bronchoscopy. Pulmonary sampling 
will be performed on day 4, 6 weeks, and 3 months following treatment. The endpoints 
of this study have been clearly defined. The investigators will determine gene transfer 
and expression via biological response and toxicity. Clinical efficacy is not a goal of this 
protocol. The proposal is straightforward and adequately addresses the issues of safety 
and vector classification. However, there is one remaining concern regarding the 
informed consent document. The consent form indicates that the patient's disease will 
be corrected. Since this protocol is a feasibility study and not an efficacy trial, only 
biological endpoints will be determined. This section of the informed consent document 
should be corrected. 
In Dr. Haselkom's absence, Dr. DeLeon noted several concerns which were outlined in 
his written review: (1) Why has the biopsy application section been omitted from the 
revised protocol? and (2) Why are the investigators administering such high titers of 
virus? Dr. DeLeon noted that the investigators have already responded to the viral titer 
question by decreasing the doses that will be administered to patients. 
Review-Dr. Zallen 
Dr. Zallen noted this protocol requires only 4 bronchoscopies; this requirement is in 
contrast to the number of procedures outlined in Dr. Crystal's protocol. The proposed 
bronchoscopies were originally going to be coupled with biopsies; however, the biopsies 
have been omitted from the revised protocol. This modification is satisfactory. Dr. 
Wilson needs to respond to Dr. Haselkom's concern regarding the risk of lung collapse 
behind the balloon and associated hypoxia. Regarding the non-human primate model, 
Dr. Zallen asked when the animals were sacrificed following the infusion of the lac/Z 
adenovirus. 
The exclusion criteria of fertile individuals was discussed previously during Dr. Crystal's 
presentation. The same guidelines are applicable for this protocol, namely, individuals 
should not be excluded based on their fertility status. Regarding the recruitment process, 
are there any concerns that these patients will feel an emotional obligation to participate 
Recombinant DNA Research, Volume 16 
[565] 
