Recombinant DMA Advisory Committee- 9/12-13/94 
patients will be post-menopausal, and Dr. Holt agreed to add this statement to the 
Informed Consent document. 
Responding to Dr. Saha’s question about choosing c -myc and c -fos as target oncogenes, 
Dr. Holt said about 15 to 20% of breast cancers have c -myc amplification. c-Myc and c- 
fos are oncogenes encoding transcriptional factors contributing to cancer cell growth. Dr. 
Holt said that the preclinical studies showed data on the level of antisense expression. 
The ratio of antisense sequences to the endogenous cellular oncogene mRNAs is 
important since antisense decreases the stability of oncogene mRNA and reduces its 
cellular levels. 
Dr. Parkman said that the preliminary tumor model data was limited to 6 mice, and that 
the study on another 20 mice is still ongoing. The data on the additional animals is 
needed for approval of the protocol. Mr. Capron suggested that Dr. Parkman review that 
data. Dr. Holt agreed to the suggestion. 
Committee Motion 
Dr. Miller made a motion to approve the protocol with a provision to provide RCR data, 
vector sequence on disks, and to revise the Informed Consent document. Dr. Parkman 
added a friendly amendment to request data on the additional 20 mice. Dr. Motulsky 
seconded the motion. Dr. Walters said that the stipulations should include deleting the 
meningeal arm of the study. 
Dr. Parkman reminded the RAC that in the future consolidated review with FDA, the 
stipulations will be approved by FDA and will not come back to the RAC. 
The RAC approved a motion made by Dr. Miller and seconded by Dr. Motulsky to accept 
the protocol submitted by Drs. Jeffrey Holt and Carlos B. Arteaga of Vanderbilt 
University, Nashville, Tennessee, by a vote of 14 in favor, 0 opposed, and 2 abstentions. 
RAC approval is contingent on the review and approval by the primary RAC reviewers of 
the following: (1) data demonstrating the absence of helper virus in a single patient dose, 
i.e., 100 ml; (2) the complete vector sequence submitted on three 3 1/2 inch diskettes in 
ASCII format; (3) a revised Informed Consent document incorporating the changes 
suggested by the RAC members; (4) deletion of the carcinomatous meningitis arm of the 
study; and (5) data from ongoing murine preclinical studies. 
Mr. Capron noted that there are no clinicians among the three primary reviewers of this 
protocol, and that several of the clinical questions brought to the discussion have been 
missed by the primary reviewers. He requested at least one clinical reviewer for every 
protocol. Dr. Wivel commented that because of the shortage of RAC members with a 
clinical background, occasionally there are not enough clinical reviewers to be assigned to 
all protocols. 
Summary 
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Recombinant DNA Research, Volume 20 
