Recombinant DNA Advisory Committee - 09/14-15/92 
Dr. Parkman asked if the size of biopsy that has been specified will be adequate to 
produce a sufficient number of fibroblasts for the injection. If an insufficient number of 
autologous fibroblasts is obtained, will allogeneic fibroblasts be used? 
Dr. Parkman inquired as to why the investigators did not choose to transduce tumor cells 
alone. For this protocol, tumor cells will have to be grown to a certain extent. Why is it 
not possible to continue to expand these tumor cells such that there is a sufficient 
number of cells to transduce? Injection of tumor cells alone would obviate the need for 
fibroblasts and eliminate concerns regarding an immune response against fibroblasts. 
Dr. D. Miller stated that he did not receive a 3Vi' diskette of the vector sequence to run 
through GenBank. The sequence must be screened for open reading frames, etc., prior 
to initiating this protocol. He asked what the effect of the irradiated transduced cells 
would be on neighboring normal cells. 
Presentation-Dr. Lotze 
In response to Dr. Zallen's question, Dr. Lotze explained that the cost of the 
thoracoscopic procedure will be incurred by the University of Pittsburgh unless it is 
performed for an entirely different purpose, such as for diagnostic purposes. Dr. Lotze 
said that he would revise the cost section such that the cost of the thoracoscopy will be 
provided as a procedure that is of no cost to the patient. 
With regard to the issue of induction of an autoimmune response, Dr. Lotze said that 
there is a large body of data demonstrating that cytokine administration does not induce 
an autoimmune response, with the exception of IL-2 induced thyroiditis. If symptoms 
occur, patients would require treatment to suppress the autoimmune phenomenon, i.e., 
steroid administration. 
Dr. Parkman added that if an immune response occurs, it may be only for the period of 
time during which there is increased IL-4 production. Since the fibroblasts are 
irradiated, the production of IL-4 will be self-limiting. Dr. Zallen asked if treatments 
administered for an autoimmune response would interfere with other antitumor therapies 
that patients might receive. Dr. Lotze responded that the patients eligible for this 
protocol have exhausted all traditional therapies for treatment of their tumor. Dr. 
Parkman stated that the reverse situation would be effected. If a patient participating in 
this protocol would require concurrent administration of steroids, this treatment would 
interfere with the effect of the experimental therapy. 
Dr. Lotze addressed the issue of using transduced tumor cells versus fibroblasts. 
Although one would hypothesize that a patient would benefit from cytokine production 
made by the cell type that is being targeted, local delivery of cytokines is normally 
Recombinant DNA Research, Volume 16 
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