The adjuvant activity of BAT antibody enables DNA vaccination to inhibit the progression of established autochthonous Her-2/neu carcinomas in BALB/c mice

• Published in: Vaccine Vol. 23; no. 25; pp. 3280 - 3287
• Main Authors: Quaglino, Elena, Mastini, Cristina, Iezzi, Manuela, Forni, Guido, Musiani, Piero, Klapper, Leah N., Hardy, Britta, Cavallo, Federica
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 09.05.2005; Elsevier; Elsevier Limited
• Subjects: 3T3 Cells; Adjuvants, Immunologic; Animals; Antibodies, Monoclonal - therapeutic use; Antibodies, Neoplasm - analysis; Antibodies, Neoplasm - biosynthesis; Applied microbiology; BAT mAb; Biological and medical sciences; Cancer; Cancer Vaccines - therapeutic use; Carcinoma - immunology; Carcinoma - pathology; Carcinoma - prevention & control; Cell growth; Cell Proliferation - drug effects; Cell Survival - drug effects; Colleges & universities; Cytotoxicity; Deoxyribonucleic acid; Disease Progression; DNA; Electroporation; Extracellular Space - immunology; Fundamental and applied biological sciences. Psychology; HER-2/neu; Image Processing, Computer-Assisted; Immunotherapy; Interferon-gamma - biosynthesis; Intravenous administration; Medical sciences; Membrane Proteins - immunology; Mice; Mice, Inbred BALB C; Microbiology; Plasmids; Rodents; Spleen - cytology; Survival Analysis; Tumors; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - therapeutic use; Italy; PBS; EC-TM; Spc; mAb; S.I; IFN; i.v; FITC; r; PE; BAT mAb; FBS; Immunotherapy; HER-2/neu; DPBS; BrdU; Carcinoma; Antibody; Rodentia; Malignant tumor; Genetic vaccine; Vertebrata; Mammalia; Mouse; Immunological adjuvant; C-Onc gene; Chiroptera
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.01.086

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 μg 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.