Recombinant DNA Advisory Committee - 06/1-2/92 
protocol is justified by the fact that it will provide valuable information concerning the 
patient's immune response after reinfusion of these transduced cells. 
Review- Dr. /alien 
Dr. Zallen stated that although she had concerns regarding the use of children as 
research subjects, Dr. Brenner assured her that neuroblastoma is a childhood tumor; 
therefore, they are the most appropriate subjects. Dr. Zallen noted that the patient 
eligibility section of the protocol states that patients must be less than 21 years of age. 
Since this is a childhood disease, this stipulation seems unnecessary. Similarly if there 
was a rare patient over the age of 21 with this disease, why should he/she be excluded 
from the protocol? 
Regarding the informed consent, Dr. Zallen suggested that someone other than the 
investigators should present this information to the patient. She noted that patients 
sometimes feel coerced to participate in a protocol when the informed consent document 
is presented by the investigator. 
Other Comments 
Dr. Leventhal asked if experiments have been performed using irradiated cells. She 
cited results obtained by other investigators using different tumor systems demonstrating 
that irradiated cells are more immunogenic than non-irradiated cells. 
Dr. Leventhal requested clarification regarding patient eligibility for other experimental 
therapies. Define the term window as stated in the protocol. Will patients continue to 
receive injections of transduced cells if they have a stable or responding disease? Will 
patients have stable or responding disease after two injections? If not, will they receive 
more injections or alternative therapy? What other treatment options are available to 
the patients? 
Dr. Post noted that Dr. Rosenberg had been granted approval to initiate gene transfer 
experiments using an IL-2 secreting vector similar to Dr. Brenner's protocol. What 
information has been reported regarding Dr. Rosenberg’s experiments? 
Dr. D. Miller asked for clarification regarding the required level of IL-2 expression for 
this protocol. Is there a theoretical basis for choosing 150 picograms per 10 6 cells in 24 
hours or is this the maximum level obtainable for these cells? 
Dr. D. Miller noted that the vector sequence had been screened for open reading frames 
and that no other open reading frames besides the neo and IL-2 coding regions were 
found. There is a question regarding the oncogenic potential of IL-2 itself. Will the IL- 
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Recombinant DNA Research, Volume 15 
