Abstract
The anti-tumor immunologic effects of plasmid DNA vaccines encoding human carcinoembryonic antigen (CEA) fused to mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) were examined. Immunization of C57BL/6 mice with the CEA-GMCSF fusion plasmids in a three injection, high-dose immunization schedule led to T cell and antibody responses specific for CEA. Mice injected with CEA-GMCSF fusion plasmids also developed IgG autoantibodies to GM-CSF. Tumor challenge with the CEA-expressing syngeneic mouse adenocarcinoma line, MC38-CEA-2, showed delayed tumor growth in mice immunized with the CEA-GMCSF fusion plasmids but complete protection in mice immunized with plasmid encoding CEA alone. In contrast, a single low-dose immunization with CEA-GMCSF fusion plasmids provided better tumor protection than low-dose CEA plasmid alone and resulted in lower titers of GM-CSF antibodies.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / immunology
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Adenocarcinoma / prevention & control
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Animals
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Autoantibodies / biosynthesis
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Autoantibodies / immunology
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Blotting, Western
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology*
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Carcinoembryonic Antigen / genetics
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Carcinoembryonic Antigen / immunology*
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Cell Line, Tumor
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Cytokines / metabolism
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Dose-Response Relationship, Immunologic
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Enzyme-Linked Immunosorbent Assay
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Female
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
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Immunization
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Immunoprecipitation
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Mice
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Mice, Inbred C57BL
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Plasmids / genetics
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Plasmids / immunology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Analysis
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Vaccines, DNA
Substances
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Autoantibodies
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Cancer Vaccines
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Carcinoembryonic Antigen
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Cytokines
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Recombinant Fusion Proteins
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Vaccines, DNA
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Granulocyte-Macrophage Colony-Stimulating Factor