Recombinant DNA Advisory Committee - 2/4/91 
Steady decline during the period after the third infusion when no cells were being 
administered. Dr. Blaese was unclear as to the difference. However, there was 
speculation about the possibility that the treatment was blocking hepatic receptors, 
although there was no data in this regard and that they will continue to look at this as 
the protocol continues. 
Dr. McGarrity asked if the PEG-ADA treatment relates in any way to the predominance 
of CD8-positive cells. Dr. Culver responded by saying that the second patient was 
slightly CD8 predominant, however, she was within normal range for a CD4:CD8 ratio 
and had varied over the course of the last few years in this regard. 
Dr. Mclvor asked if the investigators thought that the cells being infused were 
replicating. Dr. Blaese said he did not know. However, when they looked for activation 
antigens on the peripheral T cell population, a significant proportion still expressed 
HLA-DR and the IL-2 receptor at 2-3 weeks post-infusion. Therefore, either new cells 
are being recruited or cells are persisting because they begin to express these receptors 
while still in tissue culture. His guess would be that they are persisting in an activated 
state. 
Dr. McGarrity asked about the number of patients now under study. Dr. Blaese said the 
first patient was started on September 14, 1990 and the second patient was started on 
January 31, 1991. Dr. Blaese said another patient would probably be enrolled within the 
year. Dr. McGarrity asked if there had been any significant changes in the protocol. Dr. 
Blaese said no significant changes had been made. 
INTERIM REPORT ON THE HUMAN GENE THERAPY PROTOCOL ENTITLED 
"THERAPY OF PATIENTS WITH ADVANCED CANCER USING TUMOR 
INFILTRATING LYMPHOCYTES TRANSDUCED WITH THE GENE CODING FOR 
TUMOR NECROSIS FACTOR": 
Dr. Rosenberg presented an update on the TNE^jl protocol. The first two patients were 
treated six days prior to the meeting on January 29, 1991, and both were doing well. 
There was very little to report since they were only six days into the protocol but he 
would update the committee on what had transpired since the last RAC meeting. 
Dr. Rosenberg said that the protocol had come about as a result of attempts to develop 
biologic therapies for cancer patients based on adoptive transfer of immune lymphocytes 
with anticancer activity. He cited his previous research using lymphokine activated killer 
(LAK) cells administered in combination with IL-2 which produced disease regression in 
patients with melanoma and kidney cancer. One woman treated in 1985 remains 
disease-free at this time, and supports the theory that adoptive transfer of LAK cells and 
IL-2 in a small subset of patients can result in quite meaningful clinical effects. 
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Recombinant DNA Research, Volume 14 
