Recombinant DNA Advisory Committee - 2/10-11/92 
to Consider , and the non-technical abstract did not match the purpose of the protocol. The 
goal of the protocol seemed to be to track TILs and PBLs that have been genetically 
marked. At the same time, the patients will be given either IL-2 (for melanoma patients) 
or IL-2 and IFNaA (for renal cell carcinoma patients). The protocol does not adequately 
explain these procedures. There is a concern about the toxicity that was attributable to 
IL-2. It is unclear whether any of the efficacy from this treatment would be attributable to 
IL-2, and there is no comparison of this dosage of IL-2 to any other dosage of IL-2. 
Ms. Buc said the protocol does not describe the relative roles of IL-2 and IFNaA in 
comparing the TIL cells and the peripheral blood cells in terms of expected therapeutic 
effect. There is more information on the gene marking effects than on the treatment 
effects. The investigators should clarify: (1) the role of IL-2 and IFNaA; (2) whether 
therapeutic effect is expected at those dosages; (3) if the role is in some way 
complementary to other aspects of the protocol; and (4) why the consent form does not 
integrate these points in a clear manner for the patient. In the list of side effects of the 
protocol, death should be listed first instead of last or placed in a different context. 
Presentation— Dr. Economou 
Dr. Economou summarized that in some of the clinical results, it was difficult to predict 
which patients would respond to the generated TIL cell population. One patient received 
100 times more cells of the appropriate phenotype and specificity than another patient who 
received less specific cells. The first patient did not respond and the second patient 
showed a 90% reduction of liver metastases. 
Dr. Belldegrun, Dr. Economou's collaborator, spoke on the use of IL-2 and IFNaA in the 
treatment of renal cell carcinoma. This procedure sometimes results in dramatic 
antitumor activity with relatively low toxicity. Based on their studies, TILs are a 
heterogeneous population with a mixed phenotype of CD4( + ) and CD8( + ) cells. Clones 
of cells are specific for a particular tumor. However, the correct method for expanding 
this particular population is unknown. Based on the investigators' experience with 62 
patients using IL-2 and IFNaA, a protocol was initiated using a combination of TILs, IL-2, 
and IFNaA. Three of eleven patients treated on this protocol are now in complete 
remission. Based on studies with CD4( + ) and CD8( + ) heterogenous TILs, a population 
of patients with renal cancer were treated with either CD4( + ) or CD8( + ) cells alone. 
This study was the first time that a pure population of either CD4( + ) cells or CD8( + ) 
cells was infused, rather than a mixture of both populations. In vitro cytotoxicity tests, 
against autologous tumor, showed that a significant fraction of the activity resides in the 
CD8( + ) cells. This result provided the rationale for beginning clinical trials with this TIL 
cell subpopulation. The first clinical study combined CD8( + ) TIL with IL-2. The gene 
marking studies will be combined with the subpopulation studies that are currently in 
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Recombinant DNA Research, Volume 15 
