Recombinant DNA Advisory Committee- 9/12-13/94 
mentioned additional data provided by the investigators to demonstrate antitumor effect 
on established tumors in the nude mouse experiments. The tumor was established in the 
peritoneal space. The untreated animals developed a tumor size of 700 mg, and in the 
anti-myc mice, the tumor was reduced to 400 mg. In mice treated with anti-/os, the tumor 
was reduced to 100 mg. There are preliminary experiments in 6 mice, but the data is 
encouraging. 
Dr. Walters mentioned a fax letter from Dr. Haselkom stating that he was impressed with 
the recent data provided by Dr. Holt and, therefore, he would withdraw his initial 
objections to this protocol. 
Review-Mr. Capron 
Mr. Capron, in his written review, raised several questions including incomplete preclinical 
studies, spreading of vector to non-targeted cells, and effective targeting of vectors in 
human cancer. Most of these questions were addressed in the reviews by Drs. Miller and 
Haselkom. Since this study would involve a direct vector application to patients, Mr. 
Capron was concerned about any potential risk to others through vector spreading. The 
investigators responded in writing that the vector is replication incompetent and will be 
injected into a closed body cavity that should not present any risk to others. He would 
like to have clinicians on the RAC comment if treated body fluid could be released in any 
way. Mr. Capron pointed out several weaknesses of the Informed Consent document: (1) 
the format is difficult to follow because of the use of different font sizes, (2) the form 
lacks any statement on long-term follow-up, (3) the warning about not paying for injuries 
is in a small note, (4) there is an inadequate statement about withdrawing patient consent, 
and (5) the #6 item on alternative treatment is awkward. Mr. Capron said the 
investigators have addressed most of his concerns. Mr. Capron had provided specific 
wording for the Informed Consent document to address his concerns. The investigators 
have submitted a revised Informed Consent document. 
Other Comments 
Dr. Dronamraju asked how many patients will be treated. Dr. Holt said they will enroll 
10 patients. Ms. Meyers stated that there are many shortcomings in the Informed Consent 
document: other chemotherapeutic drugs for breast cancer are not mentioned under 
alternative treatments; there is no mention of contraception, autopsy, or long-term follow- 
up. Mr. Capron said that these points have been corrected in the revised Informed 
Consent document. 
Dr. Saha asked questions regarding the rationale for targeting c -fos and c -myc among 
other oncogenes, the ratio of antisense expression to the c -fos and c -myc mRNA, whether 
the antisense expression is constant from experiment to experiment, and inhibition of 
oncogene translation. Dr. Parkman asked the investigators to clarify how transduction 
efficiency will be quantitated in pleural effusions or cerebral spinal fluid (CSF). He asked 
about the time points for sampling the body fluids. 
Recombinant DNA Research, Volume 20 
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