Recombinant DNA Advisory Committee - 6/9-10/94 
the control of the present investigators. Dr. Haselkom stated that even if the vaccinia- 
CEA study fails, the CEA-DNA injection might yield positive results. Ms. Buc agreed 
with Drs. Parkman and Straus' assertion that this protocol is not approvable without 
submission of adequate preclinical data. 
Dr. Lobuglio explained that he is involved in the vaccinia-CEA study; however, the data 
is coded and the results are unknown. Dr. Miller maintained that it is illogical for the 
RAC to contingently approve a protocol based on data obtained from an experiment that 
was not reviewed by this committee. Dr. Wivel explained that the vaccinia-CEA 
experiment was considered exempt from RAC review based on the old definition of 
Footnote V-21 of the NIH Guidelines. The recently amended definition of Footnote V- 
21 would require RAC review of the vaccinia-CEA trial. 
Dr. Curiel said that this trial will provide the data regarding the safety of polynucleotide 
vaccines which hold great promise for the treatment of many infectious diseases. 
Dr. Smith asked whether the same preclinical data will be required if the investigators 
choose to treat patients with a resectable tumor rather than metastatic cancer. Dr. 
Lobuglio said that it is logical to begin this Phase I toxicity trial in subjects with 
advanced cancer. 
Dr. Straus asked whether evidence of an immune response has been observed in the 
vaccinia-CEA study. Dr. Lobuglio responded that all of the subjects in the proposed 
study have advanced cancer; therefore, any immune response observed in the vaccinia- 
CEA trial is irrelevant for the proposed study. Dr. Straus said that polynucleotide 
vaccination is a new technology currently being developed for wide applications. 
Deliberation of the proposed protocol will set a precedent for the review of future 
protocols. Dr. Straus expressed concern about establishing a precedent for approval 
without adequate preclinical data. 
Dr. Post asked whether an immune response to CEA in cancer patients is an adequate 
criterion for this study. Dr. Parkman said that a cellular immune response would be an 
adequate criterion rather than a humoral response alone. Dr. Lobuglio said that the 
vaccinia-CEA study involves immunological assays for humoral responses only. 
Committee Motion 
Dr. Haselkom made a motion to approve the protocol. Dr. Zallen made a friendly 
amendment to revise the Informed Consent document incorporating the changes 
suggested by Drs. Haselkom, Chase, and Zallen. The amendment was accepted by Dr. 
Haselkom. 
The RAC approved a motion made by Dr. Haselkom and seconded by Dr. Miller to 
accept the protocol submitted by Dr. David Curiel of the University of Alabama, 
Birmingham, Alabama, by a vote of 10 in favor, 4 opposed, and no abstentions. RAC 
approval is contingent on the review and approval by the primary RAC reviewers of a 
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Recombinant DNA Research, Volume 19 
