Human Gene Therapy Subcommittee - 11/21-22/91 
less than 5% open circular DNA in these preparations. Dr. B. Murray suggested that the 
investigators should include language in the protocol that states that the DNA will not be 
stably integrated into the cells. Dr. Nabel agreed to include this statement in addition to 
expanded information on the vector preparation. 
Subcommittee Motion 
Dr. Epstein moved to approve the protocol contingent on the following stipulations: (1) 
the informed consent document will be changed regarding inclusion/exclusion criteria; 
(2) the biopsy section of the informed consent document will be expanded; and (3) 
vector sequence will be reviewed to ensure that the issues raised by Dr. Miller have been 
satisfactorily addressed. The motion was seconded by Dr. Erickson. Dr. Mclvor 
requested that a fourth stipulation should be added to the motion regarding the inclusion 
of a detailed description of the integration status of the injected DNA. Specifically, will 
the injected DNA be integrated into the chromosomes of the tumor cells or will it be 
maintained extra-chromosomally? Dr. Nabel stated that this issue will be expanded in 
the protocol. 
Dr. Zallen asked if the investigators will be required to assay the gonadal tissues for 
possible integration into the germ line. Dr. Epstein stated that PCR would be possible 
on tissues obtained from post-menopausal females but not available from orchiectomized 
patients. Dr. Leventhal stated that a request for gonadal autopsy should be included in 
the informed consent document. Dr. Nabel agreed to include a request for autopsy in 
the informed consent document. 
Dr. Leventhal described the minimum number of biopsies that would be required to 
evaluate DNA integration. One biopsy will be required prior to each DNA/liposome 
injection. Additional biopsies at the site of the tumor would be required on days 14 and 
28 following injection. If the tumor is growing rapidly on day 14, the patient will not 
receive additional injections. If the tumor has regressed, another injection will be 
administered. 
Dr. Leventhal requested that a statement be included in the informed consent document 
which explains that the patients will receive a human antigen to which they may become 
sensitized. If sensitization to this antigen occurs, the ability of the patient to receive 
blood transfusions may be affected. 
Dr. B. Murray noted that part of the gene sequence codes for a portion of the T antigen. 
If this antigen expressed in full, could cell transformation occur? If another vector exists 
that does not code for the T antigen, why are the investigators not proposing to use this 
vector? Dr. Miller responded that the improved vector was not proposed because 
experiments have not been performed to demonstrate its efficacy. Dr. Nabel explained 
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