DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice
- 1 April 2002
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Gene Therapy
- Vol. 9 (4), 346-355
- https://doi.org/10.1038/sj.cgt.7700445
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.Keywords
This publication has 31 references indexed in Scilit:
- Liver regenerationJournal of Hepatology, 2000
- DEGRADATION OF CELL PROTEINS AND THE GENERATION OF MHC CLASS I-PRESENTED PEPTIDESAnnual Review of Immunology, 1999
- Induction of tumor antigen-specific immunity using plasmid DNA immunization in miceCancer Gene Therapy, 1999
- Expression of ?-fetoprotein and albumin genes in human hepatocellular carcinomas: Limitations in the application of the genes for targeting human hepatocellular carcinoma in gene therapyHepatology, 1998
- Origin, maturation and antigen presenting function of dendritic cellsCurrent Opinion in Immunology, 1997
- Regulation and Activities of α-FetoproteinCritical Reviews™ in Eukaryotic Gene Expression, 1997
- Intramuscular immunisation withMUC1 cDNA can protect C57 mice challenged with MUC1-expressing syngeneic mouse tumour cellsInternational Journal of Cancer, 1996
- Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.The Journal of Experimental Medicine, 1992
- Immunohistochemical characterization of inflammatory infiltrates at the site of bile duct injury in primary biliary cirrhosisLiver International, 1986
- Genetic control of alpha-fetoprotein synthesis in the mouse.The Journal of Experimental Medicine, 1977