Recombinant DNA Advisory Committee - 12/2-3/93 
obtained from this patient. Although the data suggest an increase in cytotoxic T 
lymphocyte (CTL) activity following tumor cell injections, the responses were variable. 
The reasons for this variation are unclear. Dr. Smith inquired about the numbers of 
times that patient's pretreatment level was measured. Dr. Sobol responded that this 
assay had been performed twice. Drs. Smith and Chase suggested that the variation 
observed in the data may be a result of random variation and not a result of the 
treatment. 
Dr. Sobol explained that the proposed study will provide definitive information about 
antitumor activity because of the number of patients who will be accrued. Data derived 
from this larger study will yield statistically significant results. The proposed study will 
provide useful information about autologous versus allogenic immunization. Allogeneic 
stimulation would provide a less costly approach to this treatment. 
In response to Dr. Parkman's question about the allogeneic cell line, Dr. Sobol explained 
that this tumor cell line was established from the patient treated on the previous trial. 
This allogeneic cell line will be transduced with a different retrovirus vector than was 
used for the previous trial. The new vector will produce higher levels of IL-2. 
With regard to the in vitro data, Dr. Straus asked if the variation in CTL activity and the 
clinical responses observed could be a result of the other concurrent therapies (e.g., 
steroids) the patient was receiving. Dr. Sobol answered that although the patient 
received prolonged Decadron treatment, the antitumor activity and clinical changes could 
be a result of high IL-2 expression by the transduction of cells. Dr. Straus disagreed with 
the investigator's interpretation of these results. Dr. Miller stated that these preliminary 
data are insufficient to support the proposal because the results are not interpretable. 
Dr. Carmen stated that the NIH Director should never have permitted this single patient 
protocol to be performed. No scientifically valid data can be derived from this single 
patient protocol. The investigators failed to provide evidence of preclinical efficacy in an 
appropriate animal model. 
Committee Motion 
A motion was made by Dr. Carmen and seconded by Dr. Brinckerhoff to disapprove the 
protocol. Dr. Post remarked that a relevant animal model is not available for human 
brain cancer. Dr. Sobol said some in vivo experiments had been performed in which rats 
were immunized with glial tumor cells modified to produce 11^2; however, no antitumor 
effects were observed. Dr. Straus noted that the investigators have made a great effort 
to propose an experiment designed to treat a very desperate disease; however, the 
protocol lacks sufficient preclinical data to provide a scientific basis for the study. For 
these desperate patients, many therapies are given to patients that complicate the study. 
If these alternative treatments are withheld from patients because of some false promise 
of gene therapy, the investigators could harm the patients. Lacking other supportive 
studies, Dr. Straus recommended disapproval of this study. 
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Recombinant DNA Research, Volume 18 
