4 0 CLINICAL PROTOCOL (IRB# 1456 92-12) 
A PHASE I TRIAL OF HUMAN GAMMA INTERFERON TRANSDUCED 
AUTOLOGOUS TUMOR CELLS IN PATIENTS WITH DISSEMINATED MALIGNANT 
MELANOMA 
4.1 OBJECTIVES: 
The primary objective of this protocol will be to evaluate safety, biological response, 
and survival in patients serially treated with autologous melanoma cells transduced 
with the gene for human gamma interferon (7-IFN). We will monitor the safety and 
toxicity of the treatment and will attempt to determine its immunological effects on 
the patient. We will also evaluate the clinical responses and duration of any such 
response to this treatment. 
4.2 INTRODUCTION AND BACKGROUND: 
The incidence of melanoma is steadily increasing. Cutaneous melanoma is second only 
to carcinoma of the lung in females in terms of increasing incidence. During this 
decade, approximately 1 in 90 Caucasian Americans will develop malignant melanoma. 
At the present time, the disseminated form of malignant melanoma is resistant to all 
conventional types of therapy. The ineffectiveness of hormonal therapy and 
chemotherapy has led investigators to evaluate a variety of immunotherapy regimens. 
The ultimate goal has been to consistently augment the immunological reactivity of 
melanoma patients to their own tumor. Active specific immunotherapy (treatment 
with autologous tumor cells) has been shown to be effective in some patients with 
metastatic melanoma. Berd et. al (1) immunized patients with irradiated autologous 
tumor cells and noted clinical responses in 25% of the patients treated. Other 
investigators have reported similar response rates in patients with renal cell carcinoma 
and colon carcinoma (2-4). Mitchell et. al. (5) has reported clinical responses and 
stimulation of specific cytotoxic T-lymphocytes (CTL) in patients immunized with 
autologous melanoma cells. Seigler et. al. (6-8) have serially injected high risk Stage 
I and Stage II melanoma patients using either x-irradiated melanoma cells or a 
vaccinia viral oncolysate of the tumor cells and have demonstrated improved survival 
r*3*i 
Recombinant DNA Research, Volume 17 
