Human Gene Therapy Subcommittee - 11/21-22/91 
Dr. Miller asked Dr. Economou to summarize the responses that had been seen in 
patients receiving either TIL or PBL therapy alone. The same procedures (without the 
gene marking portion of the protocol) have already been approved and performed on 
cancer patients. No data had been submitted in this protocol indicating that TIL and 
PBL therapy offer any therapeutic benefit to the patient. The investigators need to show 
data that marking studies will improve the utility of this protocol. 
Review-Dr. Leventhal 
Dr. Leventhal said that the principal concern with the protocol is the assessment of 
endpoints. There is an insufficiently detailed plan to assess the trafficking of cells. 
There should be a requirement that patients have at least one biopsiable secondary 
lesion. Urine, skin, and muscle should be assayed at least once following treatment to 
see if there was trafficking of cells to these areas. If lymphocytes are found to traffic to 
target tissues, then the therapeutic portion of this protocol could be offered to other 
patients. 
The patient eligibility portion of the protocol is unclear. The investigators state that the 
protocol will be available to patients for whom no other reasonable therapy is available. 
For melanoma and renal cell cancer, that would include any patient with metastatic 
disease. Any patient with metastatic disease should be eligible for this protocol. 
Dr. Leventhal stated that there was no relevant statistical section in the protocol to 
address the assessment of trafficking. The investigators have not explained how they will 
select the patients, collect the data, or analyze data. It is unclear which patients are 
going to be eligible for analysis at the end of treatment. 
Dr. Leventhal said that overall this protocol is very good. The investigators have 
responded to her request to separate the consent forms into two portions, a description 
of the therapeutic portion with the biomodulators and another section describing the 
gene therapy part of the protocol. The section of the consent form that describes biopsy 
of skin, muscle, and tumor should be moved from the biomodulator section to the gene 
therapy section. The reason for this suggestion is that biopsies would only be performed 
to assess trafficking of the marked cells. Dr. Walters noted that the University of 
California, Los Angeles (UCLA) Institutional Review Board (IRB) had also 
recommended that the investigators divide the consent form into a gene marking section 
and a therapy section. 
Other Comments 
Dr. Areen said that she had risk versus benefit concerns about the GINa vector. How 
would the addition of this new vector affect the patient? The investigators need to 
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