2 . 0 Specific Alms 
1. To determine whether TILs in selected patients with melanoma grown 
in combinations of IL-2 and IL-4 will lead to objective 
tumor responses in patients receiving them. 
2. To assess the ability of combinations of IL-2 and IL-4 
to cause specific TIL localization at sites of melanoma, 
using gene transduced TILS. 
3 . 0 Research Design and Methods 
3 . 1 Patient Eligibility 
1. Patients must have histologically confirmed melanoma for which standard 
curative or palliative measures do not exist or are no longer effective. These 
patients have expected survivals of six months or less. Patients previously 
treated with radiation or chemotherapy are eligible for this treatment protocol, 
but patients must have been off all treatment for at least one month prior to 
starting this therapy. 
2. Women of child bearing potential must have a negative pregnancy test. 
3. Patients must have a negtive HIV test. 
4. Patients must be free of active systemic infections and other major 
medical illnesses of the cardiovascular and respiratory systems . Only patients 
with an ECOG performance status of 0 or 1 should be placed on this protocol. 
They should have the following laboratory values : 
a. white blood cell count greater than 3000/m^ 
b. platelet count greater than 150,000/m^ 
c. bilirubin less than 1.6 mg/dl 
d. creatinine less than 1.6 mg/dl 
3 . 2 Experimental /Research Design 
(Note: in these protocols we have used International Units for units of 
IL-2 as recommended by NCI standardization requests. One Cetus unit is equal to 
6 International Units) . 
1. IL-2/IL-4 Treatments. At this time over 49 courses of IL-2/IL-4 have been 
administered. 17 patients received combination of high dose IL-2 (720,000 
lU/kg) in combination with IL-4 (10 ug/kg) without mortality and tolerable 
morbidity at the NIH. We plan to use this dose combination in patients with 
melanoma and who have not previously received either cytokine. At least a 
total of 20 patients with this malignancy, will be evaluated on this 
protocol . 
2. TIL Treatments . Selected patients with melanoma metastatic to cutaneous, 
nodal sites or other easily accessible surgical or symptomatic sites will receive 
TIL'S in addition to IL-2 and IL-4. Patients receiving autologous TIL have 
routinely received 2-3 x 10^^ cells and some patients have received as many as 
6 X lO” TIL. In the five patients shown in Tables 3 and 4 that received 
combinations of LNL6 gene-modified TIL and unmodified TIL up to 3 x 10^^ TIL were 
administered. We plan on administering TIL to 5 patients initially at low 
Recombinant DNA Research, Volume 14 
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