Human Gene Therapy Subcommittee - 11/30/90 
manner that would determine whether there is homing or merely persistence of cells 
from peripheral blood that happens to be in the tumor vasculature. 
Dr. Mclvor asked if persistence was being proposed to be studied in this protocol. 
Dr. Parkman said that one of the questions to be examined is whether ILr4, as 
another growth factor important to T cell growth, can cause enhanced T cell 
engraftment. Does IL-4 promote better homing, transmigration through endothelial 
barriers, and persistence at the site of the tumor? 
Dr. Mclvor asked how long the IL-2/IL-4 would be administered. Dr. Parkman said 
it would be for 1-2 weeks. In the Rosenberg protocol, results show that in the 
majority of patients when the IL-2 was stopped, marked TIL cells disappeared. If 
these cells persist out to approximately six weeks with the combination of IL-4, then 
the investigators could conclude that the IL-4 caused increased persistence. 
Ms. Meyers said that the section on cost and payment has not been changed in the 
revised informed consent document and asked for an interpretation on what the 
patient or his/her insurance company is expected to pay. 
Dr. Walters called on Dr. Lotze to respond to the comments of the reviewers and 
other members of the HGTS who had questions about the protocol. 
Dr. Lotze said that he had recently left the NIH to begin work at the University of 
Pittsburgh. This transition had produced problems with word processing for which 
he apologized. Furthermore, the preference of institutional review groups for 
specific wording had caused some inconsistencies in the protocol. 
Dr. Lotze said the intent of the protocol is to attempt to determine whether a 
combination of IL-2 and IL-4 improves results in TIL homing and persistence. IL-4 
has a variety of remarkable effects, one of which is to act on microvascular capillary 
endothelium. Because of this effect, IL-4 could allow improved TIL migration into 
tissues, improved persistence and growth at tumor sites, and possibly provide 
improved antitumor effects. 
Dr. Lotze noted that one major problem with TIL therapy with IL-2 alone has been 
its transient effects. The goal of this protocol is to try to add in IL-4 in order to 
increase the persistence of growth factor effects. The issues of homing keep 
recurring. There is not enough information on homing to tumor site, but this 
protocol hopes to address this issue. The best control for the proposed experiment 
would be to compare two tumors in the same individual; however, this approach is 
not possible in this patient population. The hypothetical experiment would use 
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