in patients receiving adjuvant active treatment. 
During the past 3 years, we have demonstrated that specific CTL can be generated in 
vitro by exposing patient lymphocytes to autologous tumor cells in the presence of a 
low dose interleukin-2 (9). The specific CTL have effected cell mediated killing both 
in vitro and in vivo (10,11). The killing is major histocompatability complex (MHC) 
restricted and can be generated from either peripheral blood lymphocytes or lymph 
node cells. Class I MHC proteins are involved in the presentation of intracellular 
antigens to the immune system. Thus, suboptimal levels of MHC membrane proteins 
may prevent effective presentation of tumor associated antigens. 
Recently, methods for improving anti-tumor immune responses in cancer patients by 
gene transduction of tumor cells have been proposed. A variety of lymphokine genes 
have been introduced into tumor cells using retroviral vectors (12-18). The 
transduced cells express the inserted gene and secrete the specific lymphokine. We 
have recently shown that human melanoma cells transduced with the gene for human 
7-IFN serve as potent stimulators of specific CTL (unpublished data). The 7-IFN 
gene is expressed and results in a substantial increase in the levels of Class I MHC 
protein. The MHC restricted stimulation of tumor-specific CTL is markedly 
enhanced. Gene-altered autologous melanoma cells might well provoke substantial 
post-immunological responses against host tumor burden. 
4.3 PATIENT SELECTION. 
Eligibility Criteria: 
A. Histologically confirmed diagnosis of metastatic melanoma. 
B. The patient must have one or more measurable lesions remaining after removal 
of the lesion used to prepare the cell suspension. 
C. Estimated life expectancy of at least 6 months. 
D. Age of at least 18 years. 
E. Signed informed consent. 
F. Complete recovery from effects of prior major surgery before initiating study 
participation. 
G. Adequate hematologic, renal, and hepatic function. 
Recombinant DNA Research, Volume 17 
[639] 
