Human Gene Therapy Subcommittee - 11/21-22/91 
period. T cells responsive to IL-2 in long-term cultures frequently generate melanoma- 
specific MHC-restricted cytotoxic T lymphocytes (CTL) which are different from LAK. 
Dr. Parkman asked if the CD8( + ) cells that adhere to the Cellector ® flask include 
CD56( + ) natural killer (NK) cells. The presence of CD56( + ) cells could provide a 
major variable. Dr. Belldegrun said that 99% of the cells were CD8( + ) immediately 
following selection; there was no evidence of CD56( + ) cells. However, with time in 
culture, double positives and CD56(+)/NK cells increased. Dr. Parkman stated that if 
the percentage of CD56( + ) cells increases over time in culture, then the population of 
CD8( + ) cells probably contains a combination of T and NK cells. 
Dr. Economou addressed the issue of quantitation and its role in distinguishing between 
the two vectors. There is no differentiation between ratios of 2:1 and 4:1. 
Distinguishing between 2:1 and 10 or 20:1 would demonstrate the ability to mix the two 
DNAs and pull out the relevant sequences with the primers. 
Regarding the consent form, Dr. Economou said the University of California, Los 
Angeles (UCLA), Human Subject Protection Committee was the final arbiter in this 
area. However, in reference to billing and costs, the patient should not incur out-of- 
pocket expenses. Since these procedures were based on an outpatient regimen, costs will 
be covered by grants, discretionary funds, or the patient's third party carrier. He stressed 
that the doctors are always available and assist the patients when completing the consent 
document. 
Mr. Capron asked Dr. Economou to report back to the UCLA IRB concerning the issue 
of commercialization of the patient's cell line. Dr. Economou responded that this 
concern would probably never be an issue because of the fact that the patient's cells 
would be used only as target cells; no cytokine genes will be cloned. 
Subcommittee motion 
Dr. Leventhal moved for approval of the protocol, with the following conditions: 
data regarding vector safety and testing will be submitted, reviewed, and accepted 
by Drs. Miller and Mclvor, and other members wishing to review the data; 
the protocol will be amended to include the provision that patient eligibility will 
be limited to those patients with at least one biopsiable lesion post-therapy in 
order to assess trafficking; the post-therapy assessment schedule of lesions as 
presented will be included; and the statistical section be amended to discuss how 
an analysis will be conducted to address trafficking; 
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