1 . 
TITLE 
The Treatment of Patients with Metastatic Melanoma and Renal Cell Carcinoma Using 
In Vitro Expanded and Genetically-Engineered (Neomycin Phosphotransferase) Bulk, 
CD8(+) and/or CD4(+) Tumor Infiltrating Lymphocytes and Bulk,CD8(+) and/or 
CD4( + ) Peripheral Blood Leukocytes in Combination With Recombinant Interleukin-2 
Alone, or with Recombinant Interleukin-2 and Recombinant Alpha Interferon. 
2. PROTOCOL SUMMARY 
Two groups of 20 patients each will be treated on this protocol. The first group will 
consist of patients with metastatic melanoma. The second group of patients will have 
metastatic renal cell carcinoma. Patients will be treated with various combinations of 6 
different cell effector populations: IL-2 expanded bulk tumor-infiltrating lymphocytes 
(TIL) and peripheral blood leukocytes (PBL), IL-2-expanded CD8(+)-enriched TIL and 
PBL, and IL-2 expanded CD4(+)-enriched TIL and PBL. Each group of 20 melanoma 
and 20 renal cell patients will be subdivided into 4 subgroups of 5 patients each of whom 
will receive combinations of 2 cellular effectors in the following manner: 
Subgroup A - bulk TIL + bulk PBL 
B - CD8( + )TIL + CD8(+) PBL 
C - CD4(+)TIL + CD4( + ) PBL 
D - CD8(+)TIL + CD4(+)TIL 
The novel feature of this protocol is that the two cell populations will each be transduced 
with a different retroviral vector containing the neomyciin phosphotransferase (neoR) 
gene. These replication-defective retroviral vectors - LNL6 and GIN- differ by primer 
sequences that permit them to be distinguished by polymerase chain reaction (PCR). The 
ability to "genetically mark" 2 different cell populations will permit us to address 
important questions of TIL trafficking, tumor localization and in vivo lifespan. 
Melanoma patients will be supported by a continuous infusion of recombinant IL-2 (IL-2; 
over a 4-day period for 4 consecutive weeks. This 4- week cycle may be repeated up to 
4 times with intervening 2- week rest periods. Renal cell patients will be treated in an 
identical fashion with the addition of an intramuscular or subcutaneous injection of 
interferon alpha on days 1 and 4 of each IL-2 treatment week. 
Follow-up evaluation will be performed at weeks 6, 12, 18, and 24. Post-treatment 
evaluations will be completed monthly thereafter. At periodic intervals, patients will 
have samples of blood, tumor, normal skin and normal muscle evaluated by 
semiquantitative PCR for the presence of LNL6 and GIN sequences. 
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Recombinant DNA Research, Volume 15 
