SCIENTIFIC ABSTRACT 
Scientific Abstract 
The overall objective of this study is to perform a Phase I Clinical Trial in colon carcinoma 
patients of cytokine gene transfer comprising subcutaneous immunizations with a mixture of 
irradiated autologous fibroblasts genetically modified to express the gene for IL-2 and irradiated 
autologous tumor cells. Cytokine gene transfer has resulted in significant anti-tumor immune 
responses in several animal tumor models. In these studies, the transfer of cytokine genes into 
tumor cells has reduced or abrogated the tumorigenicity of the cells after implantation into 
syngeneic hosts. We have successfully induced anti-tumor immunity in a model of colorectal 
carcinoma by immunization with a mixture of irradiated tumor cells and EL-2 transduced 
fibroblasts. Immunization with a mixture of irradiated tumor cells and EL-2 transduced cells 
induced systemic anti-tumor immunity capable of rejecting a subsequent live tumor cell challenge. 
Repeated immunizations with a mixture of irradiated tumor cells and EL-2 transduced fibroblasts 
abolished established, visible tumors in a subset of the treated animals. Colorectal carcinoma is 
one of the most common cancers in the United States and Europe with an annual incidence of 
greater than 150,000 in the U.S. Most patients are treated with tumor resection and do not have 
clinically detectable tumor following surgery. However, the majority of patients have microscopic 
metastases and eventually relapse with clinically overt disease in the liver or abdominal cavity. 
Encouraging results have been obtained with an autologous tumor vaccine as an adjuvant therapy 
following tumor resection by demonstrating an increase in disease free and total survival (Hoover 
et al., J Clin Oncol 11:390, 1993). These findings combined with the demonstration of enhanced 
anti-tumor immunity following tumor immunizations with cells genetically modified to express EL- 
2 in several animal tumor systems provide the rationale for using IL-2 gene transfer in our study. 
Patients will receive immunizations with increasing doses of IL-2 transduced fibroblasts. The 
patients will be monitored for toxicity, anti-tumor responses and the induction of anti-tumor 
immunity. The results of the Phase I trial should permit an assessment of the safety of this form 
of cytokine gene transfer and provide initial data to evaluate the potential utility of EL-2 gene 
therapy with a mixture of autologous transduced fibroblasts and irradiated tumor cells. 
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Recombinant DNA Research, Volume 18 
