Scientific Abstract 
Scientific Abstract 
Metastatic colorectal adenocarcinoma is a rapidly fatal disease in the vast majority of 
affected patients despite combined modality therapy with radiation and chemotherapy. 
Strategies have been developed to attempt to eradicate malignant cells by stimulating a 
host immune response to the aberrant colon cancer cells. In this regard, a recombinant 
vaccinia viral vector encoding human carcinoembryonic antigen (CEA), a relevant tumor- 
associated antigen, is undergoing clinical trials with the goal of eliciting CEA-specific 
immune responses. It is the purpose of this protocol to evaluate the feasibility of eliciting 
CEA-specific immunity utilizing the strategy of polynucleotide vaccination. Extensive 
work has shown that naked plasmid DNA injected into muscles is taken up by myocytes 
with expression of encoded genes. Further, the expression of these genes can elicit 
humoral and cellular immune responses to encoded antigens. We have shown in murine 
models that a CEA polynucleotide vaccine can successfully elicit antibody and T cell 
immune responses to human CEA. Further, studies have determined threshold and 
optimal dosing regimens. The CEA polynucleotide vaccine has also been demonstrated 
to protect animals against challenge with a syngeneic murine colon carcinoma line 
expressing human CEA. In this present context, we will deliver a plasmid encoding the 
cDNA for human CEA. This plasmid will be injected intramuscularly to determine 
whether anti-CEA immunity can be elicited in humans by this route. It will further be 
determined whether this route of gene transfer to humans is safe and associated with any 
toxicity. 
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Recombinant DNA Research, Volume 19 
