Electroporated DNA vaccine clears away multifocal mammary carcinomas in her-2/neu transgenic mice.
The transforming rat Her-2/neu oncogene embedded into the genome of virgin transgenic BALB/c mice (BALB-neuT) provokes the development of an invasive carcinoma in each of their 10 mammary glands. i.m. vaccination with DNA plasmids coding for the extracellular and transmembrane domains of the protein product of the Her-2/neu oncogene started when mice already display multifocal in situ carcinomas temporarily halts neoplastic progression, but all mice develop a tumor by week 43. By contrast, progressive clearance of neoplastic lesions and complete protection of all 1-year-old mice are achieved when the same plasmids are electroporated at 10-week intervals. Pathological findings, in vitro tests, and the results from the immunization of both IFN-gamma and immunoglobulin gene knockout BALB-neuT mice, and of adoptive transfer experiments, all suggest that tumor clearance rests on the combination of antibodies and IFN-gamma-releasing T cells. These findings show that an appropriate vaccine effectively inhibits the progression of multifocal preneoplastic lesions.
Quaglino
Elena
E
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Iezzi
Manuela
M
Mastini
Cristina
C
Amici
Augusto
A
Pericle
Federica
F
Di Carlo
Emma
E
Pupa
Serenella M
SM
De Giovanni
Carla
C
Spadaro
Michela
M
Curcio
Claudia
C
Lollini
Pier Luigi
PL
Musiani
Piero
P
Forni
Guido
G
Cavallo
Federica
F
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D002278:Carcinoma in Situ / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018274:Electroporation / Q000379:methods; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D016233:Immunotherapy, Active / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA