Recombinant DNA Advisory Committee - 03/1-2/93 
autologous tumor cells. Transduced tumor cells demonstrate a significant increase in the 
level of cytolytic activity. Dr. Parkman said that this data should have been provided to 
the RAC. Dr. Darrow said that these CTL responses have been melanoma antigen 
restrictive. Dr. Darrow said that he regrets that this data had not been included in their 
submission. As a point of clarification. Dr. Leventhal asked whether PBL from tumor- 
bearing patients demonstrate greater cytolytic activity against transduced autologous 
tumor cells than untransduced tumor cells. Dr. Darrow said that data indicates these 
transduced cells do generate a greater level of CTL activity than untransduced cells. 
With regard to Ms. Meyers's concern about the informed consent document. Dr. Seigler 
said that the document now states, "However, if incorporation of the virus into the tumor 
does not occur you will not be able to continue with the study." This statement along 
with the inclusion of in vitro transduction should provide clarification. Ms. Meyers 
suggested that the term "laboratory setting" be used in place of in vitro. Dr. Seigler 
agreed to the suggested change. 
Dr. Seigler stated that the patient will not be responsible for any of the costs associated 
with the experimental procedures. All other costs, including costs associated with 
treatment, will be the responsibility of the patient and/or the third-party insurance 
carrier. Immediate medical care will be provided to the patients in the event that injury 
occurs as a result of participation in the protocol. However, there is no provision for 
free medical care or monetary compensation for such injury. 
The informed consent process involves the PI, the patient, a family member, and one 
other neutral party, i.e., a nurse clinical specialist. Dr. Zallen inquired about the time 
frame that is involved in the informed consent process. Dr. Seigler stated that the 
patient has a minimum of 1 full day to consider the informed consent document and 
usually has several weeks to reconsider their decision before the procedure is initiated. 
Discussion 
Dr. Parkman asked the investigators if there are data demonstrating that 2 units of y- 
IFN is adequate to induce Class II expression. Dr. Seigler stated that 2 units is a 
minimum level of production. Of 5 tumor cell lines that have been transduced, there is 
an average of 45 units of y-IFN produced per 1 x 10 6 cell per day. Dr. Parkman asked 
Dr. Seigler what he would do if a patient's transduced cells produced only 2 units of y- 
IFN/1 x 10 6 cells/day. Dr. Seigler said he would not inject cells that demonstrated this 
minimum level of y-IFN expression. Dr. Parkman stated that the investigators should 
provide a dose-response curve demonstrating y-IFN production verses Class II 
expression. 
Dr. Parkman inquired if S + L* assays have been performed. Dr. Seigler said that these 
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