The adjuvant activity of BAT antibody enables DNA vaccination to inhibit the progression of established autochthonous Her-2/neu carcinomas in BALB/c mice.
Over the course of 33 weeks from birth, the mammary glands of virgin female BALB/c mice transgenic for the transforming rat Her-2/neu oncogene progress from atypical hyperplasia to invasive carcinoma. By week 12, all their mammary glands display many foci of in situ carcinoma. DNA vaccination at weeks 12 and 14 through in vivo electroporation of a plasmid encoding for the extracellular and transmembrane domain of the protein product of rat Her-2/neu oncogene kept 33% of mice tumor-free until week 35, when the experiment ended. To improve its efficacy the vaccine was combined with a T cell stimulatory monoclonal antibody (BAT). When each plasmid electroporation was followed by intravenous administration of 10 microg of BAT monoclonal antibody at weeks 13 and 15, 55% of mice remained tumor free (p < 0.0001) and stronger T cell and antibody-mediated immune responses were elicited. These data suggest that costimulation by BAT monoclonal antibody enables DNA vaccination to establish an effective protection against incipient carcinomas.
Quaglino
Elena
E
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Mastini
Cristina
C
Iezzi
Manuela
M
Forni
Guido
G
Musiani
Piero
P
Klapper
Leah N
LN
Hardy
Britta
B
Cavallo
Federica
F
D016475:3T3 Cells; D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D018274:Electroporation; D005110:Extracellular Space / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D007371:Interferon-gamma / Q000096:biosynthesis; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D008565:Membrane Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma