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[Cancer Research 64, 2858-2864, April 15, 2004]
© 2004 American Association for Cancer Research

Immunology

Electroporated DNA Vaccine Clears Away Multifocal Mammary Carcinomas in Her-2/neu Transgenic Mice

Elena Quaglino1, Manuela Iezzi2, Cristina Mastini1, Augusto Amici3, Federica Pericle1, Emma Di Carlo2, Serenella M. Pupa4, Carla De Giovanni5, Michela Spadaro1, Claudia Curcio1, Pier Luigi Lollini5, Piero Musiani2, Guido Forni1 and Federica Cavallo1

1 Department of Clinical and Biological Sciences, University of Turin, Orbassano; 2 Center of Excellence on Aging (CeSI), University of Chieti; 3 Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino; 4 Molecular Targeting Unit, National Cancer Institute, Milan; and 5 Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna, Italy

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.




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Copyright © 2004 by the American Association for Cancer Research.