Recombinant DNA Advisory Committee - 2/10-11/92 
Dr. R. Murray described the protocol as a Phase I clinical trial to explore the safety and 
efficacy of treating malignant tumors by incorporating the HLA-B7 antigen into the tumor 
in order in evoke a T-cell response and tumor cell killing. Another goal of this protocol is 
to determine the amount of DNA/liposome mixture that produces an optimal response 
without producing toxic side effects. 
Dr. R. Murray restated the concerns expressed previously by the HGTS in their review of 
the protocol: (1) The composition of the DNA/liposome mixture. The investigators have 
provided several publications regarding this composition. (2) The injection of the 
liposomal material into the patients' tumors and subsequent entry into the blood stream 
may cause an abnormal cardiac response. The investigators provided data from murine 
models demonstrating that there was no change observed in the heart rates or conduction 
rates following injection of the DNA/liposome mixture. (3) The status of the plasmid 
DNA used with the liposomes. The investigators have demonstrated that a majority of the 
plasmid DNA is non-linearized. It is unclear whether the immunologic response is 
improved when the plasmids are not linearized. The data indicates that an immunologic 
response is observed even when the plasmids are not stably integrated. However, there is 
concern that the DNA will be carried to other tissues if it is not linearized. The 
investigators plan to monitor DNA distribution by PCR analysis on a variety of tissue 
specimens and conduct post mortem analysis on patient's tissues. (4) The dose-response 
involves escalating injections to four groups of patients using similar volumes of 
DNA/liposome material. For each group, a different volume and injection schedule has 
been outlined over a two week period. 
Dr. R. Murray said that the patients will be closely monitored to observe whether or not 
toxic side effects occur and to determine at what point such effects would preclude the use 
of the therapy. Grade 1 and 2 toxicity levels are considered acceptable. Hopefully, at 
these levels a tumor response will be observed. In accordance with this result, there will 
be a series of biopsies to be carried out pre- and post-therapy. There was considerable 
HGTS discussion about the number of such biopsies and their timing in order to 
determine the extent of tumor regression. The integration status of the plasmid will be 
monitored. There was concern about the safety of this vector because there might be open 
reading frames that could encode oncogenes. The vector sequence was analyzed by Dr. D. 
Miller where there was no evidence of open reading frames and the proposed vector is 
relatively safe. 
The consent form has a statement about protection of confidentiality under what is called 
"other pertinent information." It states that: "We will make every effort to protect your 
confidentiality. But because of media interest, there is a significant chance that 
information concerning you and your treatment will appear publicly without your consent." 
Dr. R. Murray said there is a concern as to exactly what is meant by patient 
Recombinant DNA Research, Volume 15 
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