Human Gene Therapy Subcommittee - 11/21-22/91 
and should be approved by the subcommittee. 
Dr. Leventhal asked for clarification concerning end points for discontinuing treatment. 
How would a reaction to the HLA-B7 antibody be classified? Would this reaction be 
considered toxic or identified as a desired effect? The investigators should outline the 
stopping criteria. An analysis section should be included that would address any systemic 
responses to the HLA-B7 antigen. The informed consent document should include a 
section informing the patient of the possibility that he/she may become sensitized to the 
treatment antigen, and if blood transfusions are required, autoimmune responses may 
arise due to the presence of antibody against this antigen in the circulation. 
Dr. Leventhal noted that she did not agree with the approach that the investigators were 
proposing concerning the tumor injection schedule. The investigators plan to give 
multiple injections into the same tumor nodule. Dr. Nabel explained that the reason for 
giving multiple injections is that there are physical limitations as to how much 
DN A/liposome can be delivered into a nodule at any one time. Dr. Nabel said that he 
intends to optimize the amount of DNA delivered to the tumor by administering 
multiple injections, thereby improving transfection. The maximum volume of 
DNA/liposome complex that will be injected at one time is 0.4 milliliters. Injection 
volume would depend on the size and condition of the tumor. The number of tracks was 
the most important parameter. Although a tumor response would be welcomed, the goal 
of this experiment is to achieve the maximum tolerated levels of DNA into the tumor. 
When this level has been determined, then gene expression will be monitored in vivo. If 
gene expression is achieved in vivo, the mean response will be evaluated. 
Dr. Leventhal asked Dr. Nabel to elaborate on the biopsy regimens outlined in the 
protocol. Dr. Nabel said that the tumor nodules are to be biopsied prior to the second 
injection of DNA/liposomes. Dr. Leventhal noted that the Study Parameters section 
describes biopsies that will be performed 1 and 2 weeks, if feasible, following the initial 
injection. The statement if feasible should be eliminated from this section. It would be 
more appropriate to say that the biopsies will be required conditional on the availability 
of evaluable tumor. Dr. Nabel accepted Dr. Leventhal's rewording in this section. 
Dr. Leventhal suggested that the investigators should reexamine the experimental design 
of the protocol concerning biopsy schedules. Groups of patients could be defined in 
terms of ability to biopsy their tumor, i.e., one group of patients could be biopsied two 
weeks following the first injection while another group receives biopsies at five weeks 
post-injection. Grouping patients in this manner could yield more definitive information 
about gene expression. 
Dr. Leventhal asked Dr. Nabel if the size of the liposomes that will be used to treat 
patients is the same. Will these liposomes traffic to tissues other than the tumor into 
[246] 
Recombinant DNA Research, Volume 15 
