Recombinant DNA Advisory Committee - 03/1-2/93 
that the investigators did not provide a dose-response curve comparing the amount of y- 
IFN to the induction of Class II expression, which is one of the proposed mechanisms of 
the anti-tumor response. 
• 
Review-Ms. Meyers 
Ms. Meyers stated that the revised version of the informed consent document submitted 
by the investigators is much improved over the original; however, it still does not include 
a request for autopsy. The investigators should describe the financial obligation of the 
patient for the treatment of any adverse effects which might possibly result from the 
gene transfer procedure. 
Other Comments 
Dr. Zallen said that the informed consent document is poorly written. When the tumor 
cell transduction process is described, the investigators should explain that this procedure 
will be conducted in vitro, not in vivo. This section should also include a statement 
explaining that if the in vitro procedure is unsuccessful, then the patient will not receive 
any cell injections. The Points to Consider in the Design and Submission of Protocols for 
the Transfer of Recombinant DNA into the Genome of Human Subjects (Points to 
Consider) should be clarified with regard to potential benefits and possible adverse 
reactions. The investigators should explain the entire informed consent process at Duke 
University Medical Center. 
Dr. Post asked the investigators to provide further information about the proposed vector 
and packaging cell line. Is there homology and overlap between them? What is the 
investigators' experience with this vector and this packaging cell line? 
Dr. Miller presented a brief description of the proposed vector. This vector has a y-IFN 
coding sequence and a mutated gag start codon, ATT, which prevents gag translation. 
There is an LTR, a packaging signal that contains portions of gag, and the y-IFN gene. 
Then there is an SV40 neo R sequence at the 3' end that will be used for selection 
purposes. 
Dr. Miller said that one possible concern is that this vector produces a protein that is 
made in the gag region upstream from the CTG start codon, or glycosylated gag protein, 
which has been altered in other vectors previously been approved by the RAC. It is 
unknown what effect this protein would have on the protocol. The investigators have 
provided safety studies using this vector which indicate that this extra open reading frame 
should not be a serious concern. 
Dr. Miller said that one of the packaging cell lines that is mentioned in the protocol has 
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