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DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic mice

Cancer Gene Therapy volume 15, pages 108–114 (2008)Cite this article

Abstract

A recently developed, adaptive constant-current electroporation technique was used to immunize mice with an intramuscular injection of plasmid coding for the extracellular and transmembrane domains of the product of the rat neu664V-E oncogene protein. In wild-type BALB/c mice, plasmid electroporation at lower current settings elicits higher antibody titers, a strong cytotoxic response and completely protects all mice vaccinated with 10, 25 and 50 μg of plasmid against a lethal challenge of rat neu+ carcinoma cells. BALB/c mice transgenic for the transforming rat neu664V−E (ErbB-2, Her-2/neu) oncogene (BALB-neuT664V−E) develop an invasive mammary gland carcinoma by 20 weeks of age. Remarkably, when transgenic BALB-neuT664V−E mice were vaccinated at a 10- week interval with 50 μg of plasmid with 0.2 A electroporation, mice remained tumor free for more than a year. A single administration of plasmid associated with electroporation was enough to markedly delay carcinogenesis progression in mice with multiple microscopic invasive carcinomas, and keep about 50% of mice tumor free at one year of age. Thus, vaccination using a clinically relevant dose of plasmid encoding the extracellular and transmembrane domains of the neu oncogene delivered by electroporation prevents long-term tumor formation. These improvements in the efficacy of this cancer vaccine regimen vastly increase its chances for clinical success.

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Acknowledgements

This work was supported by grants from Italian Association for Cancer Research, the Italian Ministries for the Universities and Health, University of Torino and Compagnia di San Paolo, Turin.

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Authors and Affiliations

  1. Department of Clinical and Biological Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy

    C Curcio, M Spadaro, E Quaglino, F Cavallo & G Forni

  2. Immune Therapeutics Division, VGX Pharmaceuticals, The Woodlands, TX, USA

    A S Khan & R Draghia-Akli

  3. Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy

    A Amici

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  1. C Curcio
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  2. A S Khan
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Correspondence to R Draghia-Akli.

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Curcio, C., Khan, A., Amici, A. et al. DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic mice. Cancer Gene Ther 15, 108–114 (2008). https://doi.org/10.1038/sj.cgt.7701106

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