Recombinant DNA Advisory Committee - 03/1-2/93 
GM-CSF expression. 
The modified vector has been used with approximately 30 different cytokines. In every 
case, the modified vector performed as well as the original vector. Recently, there has 
been concern among the scientific community that the introduction of multiple antigens 
may reduce the specificity of the T cell response. In light of these concerns, the absence 
of the neo R coding region may offer an advantage. The modifications that have been 
introduced are simple and offer a theoretical safety advantage over the original vector. 
Data was presented demonstrating that there are no significant differences in gene 
transfer or GM-CSF expression between the 2 vectors. 
Dr. Post asked whether animals that receive MFG transduced cells develop an immune 
response to the GM-CSF. Dr. Mulligan said that the immune response to this protein in 
animals has not been examined in a careful fashion. Dr. Geiduschek asked Dr. Mulligan 
to describe the particular advantages of the new vector in relation to geometry, 
concentration, and the detection of helper virus breakout. Dr. Mulligan said that the 
new vector allows for very high virus titers using relatively low numbers of producer cells. 
This system allows for the possibility of preserving all of the producer cells in order to 
test for helper virus generation. These producer cells can be maintained in culture for 7 
days. 
Presentation-Dr. Simons 
Dr. Simons responded to Dr. Smith's questions about the parameters that will be used to 
monitor immune response. Dr. Simons explained that immune response will not be used 
as an endpoint for this study since this protocol is Phase I. The immunologic assays 
outlined in the protocol are merely for information purposes. The assays that will be 
used to analyze immune function in future studies are still in the developmental stages. 
The immune parameters have not yet been defined. 
In regard to the ability to establish primary cultures from these patients, Dr. Simons 
explained that Drs. Jaffe and Marshall have developed a special tissue culture medium 
which allows for the specific expansion of these primary cells. These studies have been 
performed in collaboration with Somatix Therapy, Inc. Somatix has been responsible for 
the early feasibility studies involving these primary cultures. Patients' cells have been 
routinely shipped from Johns Hopkins to Somatix, cultured, and transduced. Dr. Simons 
said that they were able to culture 11 out of 12 renal cell carcinomas and grow these 
cultures to sufficient numbers that would make the patients eligible for this study. 
Dr. Simons responded to Dr. Carmen's comments about the effect of radiation on both 
transduced and untransduced cells. When non-irradiated tumor cells are injected, these 
cells outgrow the inoculation site. The rationale for irradiation is patient safety. Data 
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Recombinant DNA Research, Volume 17 
