Recombinant DNA Advisory Committee - 12/2-3/93 
patients. 
Review— Dr. Straus 
Dr. Straus agreed with Dr. Miller's assessment about the minimal risk associated with the 
proposed study. Dr. Straus noted several initial concerns about the protocol, some of 
which were partially addressed by the Pi's written responses. Dr. Straus expressed 
concern that the proposed vector is not identical to the previously approved vector, and 
safety data on the retrovirus lots has not been submitted. The protocol states that the 
fibroblasts and tumor cells will be lethally irradiated, yet data demonstrating the level of 
irradiation required for complete cell killing has not been provided. The investigators 
have not specified the exact treatment schedule or the number of patients they propose 
to enroll on the study. In vivo evidence of an antitumor response has not been 
demonstrated in animals with established disease. The Informed Consent document is 
exceedingly brief and many items, including the number and amount of blood drawings 
and possible side effects, have been omitted. Dr. Straus concluded that the protocol in 
its present form should not be approved. 
Review-Dr. Zallen 
Dr. Zallen stated that the nontechnical abstract is unacceptable because the language is 
not comprehensible to the laypersons. She stated that her concerns focus on 3 areas: 
(1) inadequate animal model studies, (2) the capability of the investigators to conduct 
the proposed experiment, and (3) the Informed Consent document. She noted that her 
initial concern about the use of the term "immunization" in the Informed Consent 
document has been corrected in the revised document. The Risks and Discomforts 
Section of the Informed Consent document does not adequately describe the possible 
allergic reactions and risks associated with replication-competent retroviruses (RCR). 
The statement in the Informed Consent document about financial responsibility of 
research costs to the patients is unacceptable. This document should clearly state that 
neither the patients nor their insurance companies are responsible for any of the direct 
costs arising from their participation in this study. In regard to preclinical data, the 
investigators should clarify the results obtained in the animal model, e.g., why are 
systemic antitumor immune responses only obtained from injection of tumor cells in the 
opposite flank? Are there any data that demonstrates immune cell activation in an in 
vitro system? Do the investigators possess adequate expertise to reproduce the number 
of viable tumor cells required for this study? The RAC should not approve this 
experiment based on the incomplete nature of the preclinical data, the unsatisfactory 
Informed Consent document, and the high risk/benefit ratio to these patients. 
Other Comments 
Dr. Haselkom asked the investigators to summarize the information that was gained 
from the patient that was approved to receive gene transfer on a compassionate plea 
basis. Ms. Meyers suggested the inclusion of a statement in the Informed Consent 
document regarding patient confidentiality. Dr. Leventhal inquired about the process for 
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