NON-TECHNICAL ABSTRACT 
Non-Technical Abstract 
The overall objective of this study is to perform a clinical trial in colon carcinoma patients 
comprising immunizations with a mixture of irradiated skin cells genetically modified to express 
the gene for an immunostimulatory substance, termed IL-2, and irradiated tumor cells. EL-2 
gene transfer has resulted in significant anti-tumor immune responses in several animal tumor 
models. In these studies, the transfer of IL-2 genes into tumor cells has reduced or abrogated 
tumor formation after implantation into animals. We have successfully induced anti-tumor 
immunity in an animal model of colorectal carcinoma by immunization with a mixture of irradiated 
tumor cells and IL-2 transduced skin cells. Immunization with a mixture of irradiated tumor cells 
and IL-2 modified cells induced anti-tumor immunity capable of rejecting a subsequent live tumor 
cell challenge. Repeated immunizations with a mixture of irradiated tumor cells and IL-2 
modified cells 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 additional therapy following tumor resection. Immunization with tumor preparations resulted 
in a significant 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 IL-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 modified skin cells. 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 gene transfer 
and provide initial data to evaluate the potential utility of IL-2 gene therapy with a mixture of 
genetically modified skin cells and irradiated tumor cells. 
Recombinant DNA Research, Volume 18 
[629] 
