Recombinant DP^ Advisory Committee - 5/30-31/91 
Therapy Evaluation Program of the NCI as well as the FDA before the study can begin. 
Dr. Gellert noted that this was the fourth time he had reviewed this protocol (2 times before 
the HGTS and once before the RAC) and that the protocol had changed in many regards. 
He noted that at the last meeting of the HGTS the major concerns were with how the gene- 
labeled cells could be quantitated and how a denominator for that measurement could be 
obtained by assaying the total number of lymphocytes in tumor, skin and muscle. He agreed 
that the standard immunohistochemistry method could be used to at least "semi-quantitate" 
the cells to derive the denominator. However, he noted that PCR measurements of the gene- 
labeled cells at the claimed sensitivity of 1 in 10^ cells had still not been provided. He said 
that if there were contamination problems in the laboratory then samples sent to the company 
for analysis would not be usable at that level of sensitivity and therefore the interface between 
the laboratory and the company performing the PCR analysis needed to be proven. He noted 
that this could be accomplished by simply taking some comparable gene-marked cells, putting 
them into an animal system, re-isolating them and showing that the PCR assay would pick up 
down to the sensitivity level of 1 in l(r cells. 
Dr. Gellert said that in light of this lack of hard evidence he still had doubts about approving 
this protocol to move forward. 
Dr. Carmen said he felt the protocol now merited approval and that the informed consent 
document seemed to be "serviceable." He noted that the protocol in its present form is more 
readable and its intentions more focused than in previous versions. He said that the 
references that had been contained in the protocol which were irrelevant to RAC concerns 
had been removed and the gene transfer aspects of the study were enhanced. He added that 
he was persuaded that the risk of insertional mutagenesis did not warrant further scrutiny and 
that the informed consent document had been revised to address all of his previous concerns 
and that it was now much superior to its predecessor and more than sufficed for the protocol. 
Dr. Post said that this protocol was really only a small step beyond what had already been 
approved in previous marked TIL experiments, that being the administration of IL-4. He said 
it had been clarified and that in general the data package was hard to follow in that certain 
figures and tables appeared without legends and explanations. However, he felt that Dr. 
Lotze had addressed this in his presentation. He said he would still like to hear more details 
of the PCR analysis to determine whether the sensitivity issue was resolved. 
Dr. Post said one question involving the informed consent was the issue of skin and muscle 
biopsies. He said it was unclear as to what procedure would be used for obtaining these 
biopsies. 
Dr. McGarrity called on Dr. Lotze to respond to the comments of the primary reviewers. Dr. 
Lotze said that as far as the description of the skin and muscle biopsies in the informed 
consent, that at his institution it was general procedure to incorporate into a consent 
document details as to the risks associated with any procedure as well as descriptive terms of 
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