Scientific Abstract 
Scientific Abstract 
In this study, we will apply the technique of direct gene transfer to enhance immune 
response against cancer tumors in vivo. The intent of this proposed immunotherapy for 
cancer is to evaluate the clinical response to the expansion of lymphocytes which 
respond specifically to tumor antigens. 
Patients with advanced cancer who have failed conventional therapy, will undergo a 
procedure in which a plasmid DNA/lipid complex will be injected directly into the 
tumor mass. The plasmid DNA encodes the human cytokine, Interleukin-2 (IL-2), in a 
non-viral plasmid eukaryotic expression vector. 
Recombinant IL-2 protein has been approved for cancer immunotherapy in renal cell 
carcinoma, and is undergoing advanced clinical evaluation for malignant melanoma. 
The proposed study enables production of IL-2 directly in the tumor in order to’recruit 
immune cells to the tumor site, cause immunologic recognition of specific tumor 
antigens, and thus cause subsequent tumor regression. 
Increasing doses of the DNA/lipid complex will be administered to patients with a 
variety of solid tumors or lymphomas. If no toxicities are observed, the procedure will 
be repeated up to six times. The specific objectives of this study are to: 1) determine 
safety and toxicity associated with doses of this DNA /lipid complex; 2) confirm in vivo 
expression of IL-2 in tumor cells; 3) determine biological activity and pharmacokinetics 
of the treatment; and 4) determine whether expression of IL-2 gene product stimulates 
tumor regression, in patients with metastatic malignancies (either solid tumors or 
lymphomas). This immunotherapy may provide a potent therapeutic effect in cancer, 
based on a novel therapy using a well-characterized cytokine in a potentially toxicity- 
free delivery mechanism. 
Recombinant DNA Research, Volume 20 
[597] 
