Recombinant DNA Advisory Committee- 9/12-13/94 
tumor establishment and treating established tumors. 
This protocol was initially submitted to the 1994 June RAC meeting but it was 
subsequently withdrawn prior to consideration since there was a need for an executive 
session of the RAC to consider proprietary information. There was insufficient time to 
announce such a session in Federal Register. Most of the questions raised in that initial 
review have been adequately answered by the investigator. Dr. Smith had two remaining 
questions. (1) Is the radiation dose sufficient to kill the transduced autologous cell line 
while still permitting adequate expression of the transduced EL-2 gene? (2) The second 
question concerned the origin of IL-2 produced in the primary tumor cell population. The 
investigator transduced a primary cell culture established from breast cancer, which is a 
mixture of tumor cells and lymphocytes. Although most of the T-lymphocytes have been 
eliminated from the culture, the IL-2 produced could potentially originate from the 
remaining T-lymphocytes, either by lymphokine production stimulated by the transduction 
procedure or by expression of the IL-2 transgene itself. Dr. Smith asked if the investigator 
had data to show that IL-2 is produced by the transduced tumor cells. Dr. Smith said this 
information is needed for eventual scientific interpretation of the results of the trial but is 
not crucial for RAC approval of the protocol. The preclinical data is adequate to justify 
the present technology. Dr. Smith said the investigator has supplied most other data, and 
barring further discussion with respect to the specific vector, this is an approvable 
protocol. 
Review-Dr. Doi 
Dr. Doi said that he had a few questions, but that most of them had been satisfactorily 
answered by the investigator in his written response. He favored approval of the protocol. 
The questions Dr. Doi asked were as follows: (1) What is the reason for the transient 
nature of high expression (i.e., 1-3 days)? (2) Is the level of DL-2 production sufficient for 
obtaining the desired immune response? (3) Is there any control study with unmodified 
tumor cells? Is the toxicity expected to be only from IL-2 or from other "cellular" effects? 
(4) Is there any plan to inject the DNA/liposome complexes directly into tumors? and (5) 
Has the plasmid DNA vector construct been totally sequenced? 
Review-Ms. Meyers 
Ms. Meyers said her comments were all answered satisfactorily, and that the Informed 
Consent document was acceptable. 
Other Comments 
Dr. Parkman asked if there was a minimal level of IL-2 production for administration to 
patients. There is a hundredfold difference in IL-2 production between mouse cells and 
human tumor cells. Will this difference impact on clinical outcome? Dr. Smith said that 
EL-2 production in human cells is roughly at the same level in one of the animal 
experiments. Dr. Miller said the information in the submitted data regarding the IL-2 
levels is unclear. Dr. Doi asked the investigator to explain the statement in his response 
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Recombinant DNA Research, Volume 20 
