Recombinant DNA Advisory Committee - 03/1-2/93 
Dr. Walters then asked Dr. Dronamraju to present his comments on the protocol. Three 
different types of questions were raised: (1) Are the investigators proposing to use IL-2 
alone or a combination of IL-2 and IL-4 therapy? In the animal model, encouraging 
results were obtained with a combination of IL-2 plus IL-4. (2) What is the transfection 
rate in human cells and the dose necessary to elicit a CTL response? (3) How was the 
sample size of 12 patients determined. 
Other Comments 
Dr. Leventhal found this protocol to be extremely confusing. The investigators should 
address the number of tumor cells to be obtained, the end points of the study, and the 
evaluation of the tumor response in patients who already responded to chemotherapy. It 
is doubtful that any valuable information will be obtained from this study. 
Dr. Straus stated that Dr. Douglas Lowy of the National Cancer Institute has 
demonstrated that the 69% BPV genome contained in the vector can transform cells in 
vitro because the early viral genes interfere with cell cycle regulation. It is probable that 
the BPV vector will alter growth properties of tumor cells as well as normal cells. 
Ms. Meyers made several comments regarding the informed consent document including 
the financial responsibility of institutions. She requested a statement should be included 
about the fertility status of patients, both males and females, and a suggestion that 
contraception should be used during the experiment. 
This issue prompted a lengthy debate regarding the inclusion/exclusion criteria based on 
the fertility status of men and women. Dr. Miller and Ms. Buc questioned the scientific 
basis of requiring birth control during the trial. Dr. Parkman mentioned that drug 
companies are very firm on this requirement out of concern of any untoward effect to 
the fetus. Ms. Buc pointed out that contraception clauses will prevent the exclusion of 
women from protocols. Dr. Anderson added that this safeguard is good for public 
perception. In conclusion, the RAC members agreed that both men and women should 
be allowed to participate in protocols; however, they would be encouraged to use 
appropriate birth control. 
Presentation-Dr. Podack 
Dr. Podack stated that this protocol is similar to others that have used lymphokines to 
increase the immunogenicity of tumors in order to achieve an immune response that will 
be beneficial to patients. This protocol is for the treatment of SCLC. This tumor is 
particularly vicious with a mean survival of about 15 months; therefore, the potential 
benefit of this treatment outweighs the risk of the disease itself. 
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