Recombinant DNA Advisory Committee - 2/10-11/92 
Review— Dr. Leventhal 
Dr. Leventhal stated that the objective of the protocol is to study the cellular response in 
tumors that accompany infusion of lymphocytes along with interleukin-2 (IL-2). In recent 
clinical trials, cancer patients treated with lymphokine activated killer (LAK) cells and high 
doses of IL-2 have experienced complete or partial responses in the range of 20% for 
melanoma and 30% for renal cell carcinoma. The investigators want to duplicate these 
results while attempting to clarify the mechanism underlying the responses. The protocol 
would study 20 patients with melanoma and 20 patients with renal cell carcinoma. The 
patients with melanoma would be treated with IL-2 and concomitant tumor infiltrating 
lymphocyte (TIL) cell infusion. The renal carcinoma patients would also receive 
interferon alpha (IFNaA). Each group of patients would be infused with two populations 
of cells; one population would be marked with the LNL6 vector and the other with the 
GIN vector. The first subgroup would receive bulk TIL and bulk peripheral blood 
lymphocytes (PBL). The second would receive CD8( + ) TIL and CD8( + ) PBLs. The 
third group would receive CD4( + ) TIL and CD4(+) PBLs. The fourth group would 
receive CD8( + ) TIL and CD4( + ) TIL PBLs. 
The cells would be collected from the patient and grown in IL-2, in vitro, until a sufficient 
number are available for reinfusion. Tumor response and toxicity will be assessed by 
determining the level of marked cells in the patient's peripheral blood. At least one tumor 
lesion would also be measured to assess trafficking. Provisional approval of the protocol 
was granted at the last meeting of the HGTS with several requested changes. The first 
request was that data concerning vector safety and testing be submitted and reviewed by 
Drs. Miller and Mclvor, and that patient eligibility be limited to those with at least one 
lesion that could be biopsied to allow assessment of TIL trafficking. Proportionality 
experiments were requested to demonstrate the limits of ability to quantify differences in 
ratio between the two vectors. As requested, the consent form was divided into sections 
dealing with the viral markers separate from the biomodulator treatment. Dr. Leventhal 
said that the post-therapy assessment schedule of toxicity was adequate. A stopping rule 
was inserted which states, "if the data are uninterpretable the investigators will stop the 
trial." The HGTS concerns were properly addressed in the revised study. 
Dr. Kelley asked whether other investigators have shown that there is no homing of TIL 
cells to tumor tissue, making this third approach unnecessary. If this question is still 
unanswered scientifically, it ought to be pursued. Dr. Leventhal stated that Dr. Economou 
needs to address this issue in his presentation. 
Review— Ms. Buc 
Ms. Buc said that the protocol was confusing. The protocol, the consent form, the Points 
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