Recombinant DMA Advisoiy Committee - 6/9-10/94 
term 'Vaccine" throughout the protocol and the Informed Consent document, (2) 
recommendations for barrier contraception only for females and not for males, and (3) 
the legitimacy of approving simultaneous studies involving multiple cytokines. 
Other Comments 
Dr. Smith asked if the proposed dose of irradiation sufficiently prohibits proliferation yet 
maintains adequate 11^7 production. 
Dr. Parkman asked the following questions: (1) What are the results of the previously 
RAC-approved melanoma protocol involving IL-2? (2) Is there any data derived from 
preclinical animal experiments demonstrating an antitumor effect against preexisting 
tumor? Such a model would be more clinically relevant than this 10 day 
preimmunization model. 
Dr. Zallen asked how the investigators would avoid conflict of interest in eliciting 
informed consent from subjects for whom they provide care. Is there a match between 
the human leukocyte antigen (HLA) locus of the subject and the proposed cell line? 
Drs. Dronamraju and Chase asked how the investigators arrived at the proposed number 
of 5 patients per dose escalation group. Dr. Parkman asked the investigators to justify 
their choice of IL-7 over 11^3 since the data indicates that IL-3 is more effective in the 
preimmunization model. Dr. Smith inquired whether the same subjects will be targeted 
as the ongoing H^2 trial (Protocol #9309-058). If the same individuals are targeted, how 
will decisions be made regarding assignment of subjects to individual protocols? 
Investigator Responses-Drs. Economou and Overell 
Dr. Economou stated that Dr. Robert Overell of Targeted Genetics Corporation, Seattle, 
Washington, would respond to questions regarding cell bank certification, toxicology 
studies, and inclusion of the HSV-TK gene. In response to Dr. Doi's question regarding 
the autologous arm of the study. Dr. Economou said that a success rate of 90% has been 
achieved in establishing primary cultures from melanoma patients. Transduction of these 
cells results in a level of 11^7 production between 10 and 50 ng 11^7/1 x 10^ cells/24 
hours. There will be no attempt to clone high producing autologous cells. 1,000 ng DL- 
7/1 X 10^ cells/24 hours will be the upper limit for 11^7 production. Bulk transduced 
cells will be selected for hygromycin resistance and are expected to produce 11^7 within 
the range of between 10 and 50 ng/24 hours. In the allogeneic arm of the protocol, 
doses of 10, 100, and 1,000 ng 11^7/24 hours will be achieved. The immunological 
response will be determined and compared to the autologous tumor cell data in which 
ID-7 production is variable. 
Regarding Ms. Meyers' concerns. Dr. Economou stated that both male and female 
patients would be counselled with regard to contraception. Premenopausal women must 
have had a negative pregnancy test prior to entering the study. 
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Recombinant DNA Research, Volume 19 
