Human Gene Therapy Subcommittee - 11/21-22/91 
answered in the human situation. 
Dr. Parkman stated that the investigators have not specified the types of tumors that 
would be proposed for treatment in this study. This protocol should limit treatment to 
melanomas since this type of tumor is immunologically distinct, offering potential 
therapeutic benefit, in addition to the ability to monitor the effects of treatment on 
distant sites. Another concern is that the in vivo animal data were generated using naive 
animals. Although immunotherapy has never been proven as an effective treatment 
against bulk disease, it would be efficacious to show a systemic effect of the therapy on 
microscopic disease. Animal models exist to study the effects on microscopic disease, 
e.g., lung metastases. Although the investigators are doing a Phase I study, there still 
must be justification that the protocol has the likelihood of being effective. 
Dr. Parkman summarized the areas in which there was insufficient information or data: 
(1) What are the tumor types proposed for treatment? (2) Is IL-2 secretion by 
fibroblasts plus irradiated tumor cells equivalent to the levels observed in viable tumor 
cells? (3) Is tumor cell replication necessary to obtain the ultimate protective effect of 
the therapy? (4) Data should be provided in an appropriate animal model that is more 
analogous to the human setting, i.e., skin fibroblasts, irradiated tumor cells, and pre- 
existing tumor burden. 
Review-Dr. Neiman 
Dr. Neiman stated that many of his concerns had been addressed by Dr. Parkman. 
Although the protocol addresses a potentially important issue in terms of broadening the 
applicability of a new approach to tumor immunotherapy, the preclinical testing in terms 
of animal models and vectorology are short of the standards that have been established 
for similar protocols. The investigators need to perform additional experiments that will: 
(1) demonstrate an effect on the type of tumor cells being proposed for the human 
setting using skin-derived fibroblasts; (2) demonstrate adequate production of IL-2 from 
these transduced cells in the mixture setting, (3) demonstrate an adequate immune 
response in an appropriate animal model, and (4) identify the types of human tumors 
that will be targets for this therapy. 
Review-Mr. Capron 
Mr. Capron asked what the statement "fail conventional therapy" actually refers to in the 
protocol. The criteria needs to be defined more clearly. What does the statement mean 
that "patients will come from those who are referred by physicians and those who are 
self-referred?" The informed consent document states "there may be no direct benefit 
from the therapy to the subject." The word "research" should be used in place of 
"therapy." He stated that the word "vaccination" is used throughout the document and 
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