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Characterization of a Messenger RNA Polynucleotide Vaccine Vector¹

Department of Medicine and Gene Therapy Program, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300

We have constructed mRNA transcripts encoding luciferase and human carcinoembryonic antigen (CEA) which are capped, polyadenylated, and stabilized by human ß-globin 5' and 3' untranslated regions. The mRNA construct encoding human CEA directed CEA expression in mouse fibroblasts in vitro following liposome-mediated transfection. The luciferase encoding mRNA transcripts mediated luciferase expression in vivo following i.m. injection. Based on the demonstration of protein expression in vitro and in vivo, the feasibility of using such a vector as a tumor vaccine was examined. In this pilot study, seven mice received 50 µg mRNA transcripts encoding CEA twice weekly for 5 weeks by i.m. injection followed by challenge with syngeneic, CEA-expressing tumor cells. This dose and schedule "primed" an immune response to CEA. Five of seven mRNA-immunized mice demonstrated anti-CEA antibody 3 weeks after tumor challenge whereas control mice had no evidence of antibody response. This strategy might be particularly useful to induce an immune response to a proto-oncogene product or growth factor which poses a risk of inducing malignant transformation consequent to prolonged protein expression.

¹ Supported by a grant from Herman and Emmie Bolden as well as the American Cancer Society.

² To whom requests for reprints should be addressed, at Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, AL 35294-3300.

Received 12/ 7/94. Accepted 2/16/95.

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