Human Gene Therapy Subcommittee - 11/21-22/91 
to the timing of cultures. Renal TIL demonstrate an increase in CD4( + ) rather than 
CD8( + ) populations. On a clonal level, CD8( + ) clones are highly specific against renal 
cell carcinoma. However, these clones are the minority, and this effect cannot be 
demonstrated in the bulk population. 
Ten renal cell carcinoma patients have been treated with various combinations of TIL, 
IL-2, and a-IFN. In every patient treated, TIL were expanded to between 10 10 and 10 11 
total cells. In each patient, the TIL that were generated exhibited varying percentages of 
CD4(+) or CD8( + ) cell populations, all of which were expanded in IL-2. All TIL 
derived from these patients demonstrated a high level of cytotoxicity against autologous 
tumor cells in vitro. A wide range of responses to this therapy was observed. Some of 
the renal cell carcinoma patients exhibited no response while two patients showed 
complete remission of all tumor sites. 
Based on the results of this study, Dr. Belldegrun said that a new protocol was initiated 
(in collaboration with Applied Immune Science of Menlo Park, CA) looking at the 
administration of CD8( + ) TIL subpopulations for the treatment of renal carcinoma. 
Nine patients were studied, using the Cellector® T-150, a selection flask that provides a 
mean purity of 97% CD8( + ) cells. Cells were successfully expanded from all patients 
that were more than 95% CD8( + ). Autologous tumor killing was contained in this 
fraction. A Phase I/II study was then initiated using a combination of CD8( + ) renal 
TIL and IL-2. 
Dr. Economou addressed the biologic and safety issues of the new retroviral vector 
GINa. GINa has passed all of the safety tests that had been required by the HGTS and 
RAC for previously approved vectors. The only test pending is for mycoplasma, and 
these data should be obtained in a few weeks. Dr. Economou said that he would 
forward the mycoplasma data to Dr. Miller when it became available, along with helper 
virus data. 
Discussion 
Dr. Miller asked if GINa had been screened for bovine diarrheal virus and porcine virus. 
Dr. Robert Moen of Genetic Therapy, Inc. (GTI), replied the GINa vector had been 
submitted to those tests and the results were consistent with those already approved by 
the HGTS. Dr. Miller requested a list of the tests that had been performed. Dr. 
Leventhal asked that dates be included with that list, as well as the number of lots 
tested. Dr. Miller requested data on the number of mice and hamsters that had been 
injected, the volume of supernatant, and whether any positives occurred. He would like 
to examine all of the documentation that the investigators submitted to the master file 
for the FDA. Dr. Moen said the documentation given to the FDA could be supplied 
either in toto or in condensed form. 
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