Recombinant DNA Advisory Committee - 09/9-10/93 
tumorigenicity of these cells. Data demonstrate that no detectable cells ( < 1 in 7 x 10 6 
cells) survive following lethal irradiation. In his primary review, Dr. Miller questioned 
whether it is adequate to irradiate tumor cells at 6,000 rad for the human trial while in 
preclinical studies, data were obtained using 12,000 rad irradiation. The investigators 
responded to Dr. Miller's concerns stating that 12,000 rad will be used for the human 
study. Dr. Miller expressed satisfaction with the Pi's response. 
Review— Dr. Haselkorn 
Dr. Haselkorn stated that the investigators have provided data demonstrating that the 
irradiation schedule for the transfected cells is sufficient to inhibit proliferation of 
clonogenic cells while retaining their ability to express 11^2. Dr. Haselkorn said that he 
had solicited the expert opinion of Dr. Lou I .aim ins of the University of Chicago, 
regarding the BPV vector. Dr. Laimins questioned the investigators' assumption that the 
BPV vector is maintained as an episome at high copy number in transfected human 
tumor cells and that high level IL-2 production is facilitated. Dr. Laimins notes that 
while BPV plasmids transfected into mouse cells can be maintained as episomes, BPV 
usually integrates into human chromosomes. Therefore, the BPV vector demonstrates no 
advantage over retrovirus vectors. Dr. Haselkorn questioned whether the BPV vector 
actually expresses higher levels of IL-2 than retrovirus vectors. 
Review-Dr. Secundy 
Dr. Secundy stated that her comments were primarily confined to the Informed Consent 
document. Most of her initial concerns about the discrepancy between the gene therapy 
description in the protocol versus the Informed Consent document have been corrected. 
One remaining concern is the statements regarding third party payer reimbursement for 
research related injuries in Section 4.7 of the protocol and the Informed Consent 
document. The responsibilities for the financial burden must be clarified. 
Other Comments 
Dr. Walters summarized written comments submitted by Dr. Smith concerning: (1) a 
discrepancy between the dose of radiation used for the transfected cells versus the dose 
proposed for the clinical study, and (2) a discrepancy in the data regarding the success 
rate of growing SCLC cells in vitro. One statement refers to a 70% success rate versus a 
30% success rate stated elsewhere in the protocol. 
Dr. Geiduschek expressed his concern about the episomal status of the BPV vector 
within transfected cells and the levels of IL-2 production. Dr. Miller stated that the issue 
of whether the vector is episomal or integrated is irrelevant since the investigators have 
demonstrated high level ID2 production in transfected cells. Dr. Post suggested that the 
RAC should stipulate a minimum level of IL-2 production for cells to be administered to 
the patients. 
Investigator Response-Drs. Podack and Cassileth 
Recombinant DNA Research, Volume 18 
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