A DNA vaccine encoding genetic fusions of carcinoembryonic antigen (CEA) and granulocyte/macrophage colony-stimulating factor (GM-CSF)

Vaccine. 2005 Jan 26;23(10):1273-83. doi: 10.1016/j.vaccine.2004.08.043.

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

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / prevention & control
  • Animals
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • Blotting, Western
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Immunization
  • Immunoprecipitation
  • Mice
  • Mice, Inbred C57BL
  • Plasmids / genetics
  • Plasmids / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Vaccines, DNA

Substances

  • Autoantibodies
  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Cytokines
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Granulocyte-Macrophage Colony-Stimulating Factor