Jeffery Marks, Ph.D. 
Duke University Medical Center 
Box 2873 
Durham, NC 27710 
Tel: (919) 684-5028 
Ramila Philip, Ph.D. 
Applied Immune Sciences 
5301 Patrick Henry Drive 
Santa Clara, CA 95054-1114 
Tel: (408) 980-5935 
Fax: (408) 980-5888 
1.0 TITLE 
A Pilot Study of Autologous Human Interleukin 2 (11-2) Gene Modified 
Tumor Cells In Patients with Refractory or Recurrent Metastatic Breast 
Cancer 
2.0 BACKGROUND AND RATIONALE 
2.1 Background Information - Breast Cancer 
The incidence of breast cancer is steadily increasing. 
Approximately 1 in 8 American women will develop breast 
cancer. Refractory metastatic breast cancer has a grim prognosis. 
With conventional chemotherapy and radiation therapy, less 
than 5% of patients are long term survivors. 
At the present time, the metastatic form of breast cancer that has 
failed all conventional types of therapy has a poor prognosis. 
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 breast cancer patients to their 
own tumor. In other human tumor systems, active specific 
immunotherapy (treatment with autologous tumor cells) has 
been shown to be effective in some patients with metastatic 
disease. 
2.2 Active Immune Therapy 
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 
[ 248 ] 
Recombinant DNA Research, Volume 20 
