A DNA vaccine encoding genetic fusions of carcinoembryonic antigen (CEA) and granulocyte/macrophage colony-stimulating factor (GM-CSF).
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.
Lima
Jose
J
Division of Hematology and Oncology, Department of Medicine, and the Comprehensive Cancer Center, University of Alabama at Birmingham, WTI 558, 1824 6th Avenue South, Birmingham, AL 35294-3300, USA.
Jenkins
Connie
C
Guerrero
Antonio
A
Triozzi
Pierre L
PL
Shaw
Denise R
DR
Strong
Theresa V
TV
D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D019444:Vaccines, DNA
D001323:Autoantibodies; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor