Recombinant DNA Advisory Committee - 06/7-8/93 
respond to these questions, he would recommend approval of this protocol. 
Review-Dr. Brinckerhoff 
Dr. Brinckerhoff agreed with Dr. Doi's assessment of the protocol. She noted that the 
investigators have not provided an extensive summary of previous results. The PI should 
explain whether the large doses of liposome that will be administered by catheter to the 
patients is safe. She stated that the investigators adequately responded to her written 
comments and that she recommends approval of the protocol. 
Review-Dr. Secundy (Presented by Dr. Brinckerhoff) 
In Dr. Secundy's absence, Dr. Brinckerhoff summarized her written review. Dr. Secundy 
states that in the Informed Consent document should be clarified and written in 
simplified language. In addition, the Alternative Therapies section should be clarified. 
Other Comments 
Ms. Grossman asked whether this protocol is an extension or a replacement of the 
previous study, and a description of the types of tumors that will be treated. Dr. Carmen 
asked whether the 11^2 that will be administered refers to the gene or the gene product. 
Ms. Meyers suggested that the Informed Consent document should recommend male and 
female contraception and include a request for autopsy. Dr. Miller stated that the vector 
sequence was checked through GenBank, and that there are no harmful sequences or 
open reading frames that pose any concern. Dr. Geiduschek asked the PI to comment 
on the comparative merit of liposome delivery versus retrovirus vector in regard to 
technical issues such as transduction efficiency, mitotic state of target cells, etc. Dr. 
Krogstad asked the PI to elaborate on the animal data. 
Investigator Response-Dr. Nabel 
Dr. Nabel explained that this study is a new protocol, not the extension of the previous 
protocol. Intratumoral injection of liposome complexes is currently used in the 
treatment of melanoma. When catheter-based delivery is employed, other tumor types 
will be targeted that have a well-defined vascular blood supply, e.g., hepatic tumors. 
Animal studies indicate that DMRIE/DOPE is more efficacious and less toxic than the 
liposome preparation used in the previous trial. There have been no adverse effects 
associated with the old liposome preparations. The new liposome-foreign MHC gene 
preparation provides protection in animals. At 1,000-fold higher doses of the new 
preparation, no toxicity is observed. He explained that much higher doses of the new 
vector will be obtainable. 
Dr. Nabel summarized previous results from 5 melanoma patients. The clinical 
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