neoplasms. T cells isolated from lymph nodes, peripheral blood lymphocytes, 
or tumor infiltrating lymphocytes (TIL) reacted against melanoma in patients 
receiving various forms of immunotherapy. The specificity of the T cell 
response was directed against a common MAA. 
2.7 Rationale: The objective is to determine if immunization of Stage IV 
malignant melanoma patients with an IL-2-secreting allogeneic melanoma cell- 
line is tolerated without evident toxicity. The use of established cell-lines 
by-passes the necessity of modifying autologous tumor cells for each patient. 
Growing autologous tumor cells in cell culture can be a technically difficult 
and is not always successful. The emergent cells may be a non representative 
subline. Our laboratories established a melanoma cell-line from a patient 
with malignant melanoma (see below for details) . Recent evidence, both in our 
laboratory and in the laboratories of other investigators, indicates that IL-2 
secretion by tumor cells increases the frequency of tumor specific cytotoxic 
precursors and cytotoxic T lymphocytes. 
2.8 The melanoma cell-line: Characteristics of the melanoma cell-line (UISO- 
MEL-4 ) are presented in Table 5. 
2.9 Clinical Protocol: This is a pilot study of immunization with allogeneic 
melanoma cells that have been modified to secrete IL-2. They will be injected 
into selected patients with Stage IV metastatic melanoma who differ at three 
of six alleles specified by the MHC Class I locus. The expected duration for 
the trial is 12-15 months. The safety of the procedure will be established 
during this period. 
The melanoma cells were transduced with the retroviral vector pZipNeoSVIL-2 . 
The IL-2-secreting cells will be irradiated (5,000 rads) and administered in a 
series of four immunizations. If a patient has a response, as defined in 
section 10.0, then additional immunizations will be administered for up to one 
year in duration or until the disease progresses. Six patients will receive a 
5 x 10 cells intramuscularly + 2 x 10 cells intradermally (2 injections), 
and the remaining six will receive a one log higher number of cells (see 
section 7.1). 
3.0 Criteria for Patient Eligibility 
Patients must fulfill the following criteria to be eligible for admission to 
the study: 
3.1 Histologic confirmation of metastatic malignant melanoma at the University 
of Illinois, Department of Pathology. 
3.2 Stage IV disease that can not be controlled by conventional therapy. 
3.3 Measurable or evaluable disease. 
3.4 Karnofsky performance status > 70% and life expectancy > four months 
(Appendix II) . 
3.5 Adequate hematologic function, with WBC > 3000/mm , absolute lymphocyte 
count > 1000/mm^, hemoglobin > 9, and platelets > 100,000/mm^. 
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Recombinant DNA Research, Volume 18 
