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DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice

Cancer Gene Therapy volume 9, pages 346–355 (2002)Cite this article

Abstract

The oncofetal alpha-fetoprotein (AFP) is reexpressed in the majority of hepatocellular carcinomas and may be used as a target molecule for an immunotherapy or prophylaxis against this tumor. We investigated the potential of DNA vaccination with AFP-expressing plasmid DNA to induce an immune response against AFP-expressing tumor cells in DBA/2 mice. 62.5% of mice vaccinated with AFP-expressing plasmid DNA, rejected subcutaneous syngeneic AFP-expressing P815 tumors, whereas only 16.7% of mice vaccinated with control plasmid rejected these tumor cells (P=.03). Mean survival of mice after challenge with subcutaneous AFP-expressing tumor cells was prolonged for 8 days in mice vaccinated with AFP-expressing DNA (35 days) compared to mice vaccinated with control plasmid (27 days). To rule out possible autoimmune reactions against regenerating liver, which also reexpresses AFP, we evaluated the influence of AFP-specific DNA vaccination on liver regeneration in DBA/2 mice. Histologic quantification of proliferating hepatocytes and of the amount of necrotic liver tissue in carbon tetrachloride–damaged liver did not reveal statistically significant differences in mice vaccinated with AFP-expressing plasmid compared to control mice. These data suggest that AFP-specific DNA vaccination represents a useful tool to inhibit growth of AFP-expressing tumors in mice that does not affect liver regeneration.

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Acknowledgements

This work was funded by Grant 01GE9613/8 of the German Research Ministry BMBF and a Bonfor Grant 107/58 of the University of Bonn to WHC. We thank Jörg Reimann and Reinhold Schirmbeck, Institute of Medical Microbiology, Ulm, Germany, for helpful discussion concerning the detection of CTLs and for providing the cytokine-expressing plasmids. We thank Olaf Wilke for technical assistance in mouse experiments.

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Authors and Affiliations

  1. Department of Medicine I, University of Bonn, Bonn, Germany

    Petra Hanke, Matthias Serwe, Tilman Sauerbruch & Wolfgang H Caselmann

  2. Institute of Pathology, University of Bonn, Bonn, Germany

    Frank Dombrowski

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  1. Petra Hanke
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Correspondence to Wolfgang H Caselmann.

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Hanke, P., Serwe, M., Dombrowski, F. et al. DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice. Cancer Gene Ther 9, 346–355 (2002). https://doi.org/10.1038/sj.cgt.7700445

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