Recombinant DNA Advisory Committee - 3/3-4/94 
activity of the transduced cells will be obtained. Dr. Hirano questioned whether the 
study design will allow acquisition of statistically significant efficacy data; and if the 
primary objective is toxicity assessment, why are so many patients needed. Dr. Walker 
said that according to the suggestion by his consulting statistician, some statistically 
significant information regarding efficacy may be obtained by increasing the number of 
patients from 24 to 40 during the second treatment period. There are many identical 
twins interested in participating in this study; therefore, recruitment is not a serious 
problem. 
Dr. Smith asked about the number of twins who have developed AIDS. Dr. Walker 
answered that approximately one-third of these subjects have CD4 counts below 200, 
one-third between 200-500, and one-third above 500. 
Dr. Walker responded to the suggestions outlined in Mr. Brave rman's written comments. 
A statement will be included in the Informed Consent document that advises patients 
that their participation in this protocol may exclude them from other vaccine 
immunotherapy or gene therapy studies. With regard to the willingness of subjects to 
participate in the control group of this study, Dr. Walker explained that once the safety 
issues have been resolved, protocols will be developed to examine efficacy. Patients in 
the control arm will receive untransduced CD8( + ) cells. A companion protocol is in 
progress that specifically addresses the issue of lymph node biopsy; therefore, subjects 
will not be excluded from the study if they refuse such biopsies. Tonsil biopsy will be 
considered for the present study. Dr. Walker did not agree to lower the age of patients 
from 18 to 13 since this protocol is not a pediatric study. Regarding the question posed 
by Dr. Parkman about the management of possible encephalopathy, Dr, Walker 
responded that an immediate plan has not yet been established for such possible side 
effects; however, standard medical practices would be implemented. 
Dr. Zsebo of Cell Genesys, Inc., Foster City, California, responded to the question on 
the animal model experiment. Dr. Zsebo said that this experiment was designed to 
obtain information about efficacy and safety. Two types of experiments have been 
performed. Tumors were established in nude mice with tumor cells transduced to 
express the HIV envelope proteins. These tumors were challenged by infusion of mouse 
T cells transduced with the hybrid CD4 receptor gene. In another experiment, tumor 
cells and transduced T cells were mixed prior to implantation in nude mice. 
Notwithstanding the interaction of these two types of cells, no overt inflammatory 
response was observed. Dr. Zsebo speculated that a probable reason for the negative 
result might be that not all tumor cells implanted in nude mice were transduced and 
expressed HIV envelope proteins, rendering them susceptible to cell killing by T cells 
transduced with the hybrid receptor. Attempts will be made to purify the tumor cells 
expressing the HIV envelope proteins before implantation in nude mice in order to 
repeat these experiments. Dr. Post asked whether there is any evidence to indicate that 
the transduced T cells, which are present in blood circulation, are activated by the HIV 
proteins expressed on cells in the tumor mass. Dr. Zsebo conceded that this result is a 
potential shortcoming of the present model. Some other primate and severe combined 
immunodeficiency mouse models will be considered, but there is no satisfactory animal 
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Recombinant DNA Research, Volume 19 
