Recombinant DNA Advisory Committee - 2/10-11/92 
the DNA. 
Dr. R. Murray restated his concern regarding the protection and confidentiality of the 
patient in the consent form. Dr. Nabel responded that it is best to acknowledge the 
possibility that the patients' identities might become public; however, every attempt will be 
made to protect their identity. Dr. R. Murray asked if the patients would be in a clinical 
research unit. Dr. Nabel answered that for the most part patients would be treated as 
outpatients. 
Dr. Haselkom asked how the investigators would evaluate the optimal composition of the 
DNA/liposome complex. Dr. Nabel said that each time a new batch of DNA/liposomes is 
prepared, the investigators have titered it on human melanoma and other lines. So far, the 
results have been very reproducible. As a result of these studies, 1 microgram of DNA 
and 7.5 nanograms of liposomes are routinely used; this quantity allows for optimal 
infection of a variety of cell types. 
Dr. Haselkom asked if HLA-B7 expression has been studied in mice. Dr. Nabel 
responded that the investigators have been unsuccessful in expressing this antigen. Dr. 
Haselkom asked about transport of the DNA into the central nervous system and multiple 
sclerosis in autoimmune disease. Dr. Nabel said that PCR analysis of brain tissue has 
been performed, as well as in situ autoradiography, and low levels of plasmid were found 
with no pathology in the brain. Dr. Haselkom then asked whether Dr. Nabel would be 
doing an immunization with HLA-B7. Dr. Nabel said that preimmunization would not be 
performed in these Phase I studies. Preimmunization would not allow an immune 
response to HLA-B7 to be used as an indicator of gene expression. 
Dr. Carmen requested that the following wording be changed in the consent form. Dr. 
Nabel agreed. The wording reads as follows: 
"By using techniques in the laboratory it is now possible to prepare large amounts of 
human DNA or genetic material in bacteria. This DNA will be mixed with fat 
bodies called liposomes, and we plan to transport the mixture into your tumor by a 
bacterial carrier or delivery system. Also included in this package is a separate 
bacterial gene which helps us trace the location of the DNA/liposome mixture. 
Once introduced into the tumor the DNA produces a protein which stimulates tissue 
rejection. This protein, known as HLA-B7, causes the cells which will contain it to 
be recognized as a foreign enemy by your immune system. The purpose of our 
study is to determine whether this treatment will induce the cells of your immune 
system, known as lymphocytes, to attack and kill your tumor." 
Dr. Krogstad asked about the other cells that will be transfected and that express the 
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