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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-04, Vol.64 (8), p.2858-2864
Main Authors: QUAGLINO, Elena, IEZZI, Manuela, LOLLINI, Pier Luigi, MUSIANI, Piero, FORNI, Guido, CAVALLO, Federica, MASTINI, Cristina, AMICI, Augusto, PERICLE, Federica, DI CARLO, Emma, PUPA, Serenella M, DE GIOVANNI, Carla, SPADARO, Michela, CURCIO, Claudia
Format: Article
Language:English
Subjects:
Animals
Antibody-Dependent Cell Cytotoxicity
Antineoplastic agents
Biological and medical sciences
Carcinoma in Situ - genetics
Carcinoma in Situ - immunology
Carcinoma in Situ - therapy
Electroporation - methods
Female
Genes, erbB-2 - genetics
Immunotherapy, Active - methods
Immunotherapy, Adoptive - methods
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - immunology
Mammary Neoplasms, Experimental - therapy
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Pharmacology. Drug treatments
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - immunology
T-Lymphocytes, Cytotoxic - immunology
Tumors
Vaccines, DNA - administration & dosage
Vaccines, DNA - genetics
Vaccines, DNA - immunology
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-03-2962