Journal
CANCER GENE THERAPY
Volume 9, Issue 4, Pages 346-355Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cgt.7700445
Keywords
DNA vaccination; hepatocellular carcinoma; alpha-fetoprotein; liver regeneration
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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 AP-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 AR-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 AR-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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