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Gene Therapy Program, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294 [R, M. C., A. F. L., F. L., S. E. M., L. A. S., D. L. B., D. T. C.], and Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892 [J. K., J. S., S. A.]
We have constructed a DNA plasmid encoding the full length complementary DNA for human carcinoembryonic antigen (CEA) driven by the cytomegalovirus early promoter/enhancer (plasmid DNA encoding human CEA) and demonstrated that this plasmid can function as a polynucleotide vaccine. This polynucleotide vaccine induced humoral and/or cellular immune responses specific for human CEA in all 5 immunized mice. Lymphoblastic transformation data with the use of enriched T-cell populations detected the presence of CEA-specific memory T-cells in 3 of 5 mice. Lymphocytes from 2 of 5 mice had interleukin 2/interleukin 4 release in response to CEA. CEA specificity was confirmed by the absence of reactivity to a control antigen and lack of CEA reactivity among mice vaccinated with a control plasmid encoding chloramphenicol acetyltransferase. Four of 5 mice vaccinated with plasmid DNA encoding human CEA demonstrated anti-CEA antibody responses. This immune response compared favorably with a positive control group of mice immunized with vaccinia-CEA by a dose and schedule previously shown to induce immunoprotection and therapy against a human CEA expressing syngeneic murine colon carcinoma model. Studies are ongoing to establish the construct, dose, and schedule to elicit optimal CEA-specific immune response as well as immunoprotection and therapy against human CEA expressing syngeneic murine adenocarcinoma models.
1 To whom requests for reprints should be addressed, at University of Alabama at Birmingham Comprehensive Cancer Center, 1824 6th Avenue South, Birmingham, AL 35294-3300.
Received 12/16/93. Accepted 1/20/93.
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