1. ¹Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
2. ²VGX Pharmaceuticals, Immune Therapeutics Division, The Woodlands, TX, USA
3. ³Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy

Correspondence: Dr R Draghia-Akli, VGX Pharmaceuticals, Immune Therapeutics Division, 2700 Research Forest Drive, Suite 180, The Woodlands, TX 77381, USA. E-mail: rdraghia@vgxp.com

Received 9 April 2007; Revised 13 August 2007; Accepted 18 August 2007; Published online 9 November 2007.

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 neu^664V-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 g of plasmid against a lethal challenge of rat neu⁺ carcinoma cells. BALB/c mice transgenic for the transforming rat neu^664V-E (ErbB-2, Her-2/neu) oncogene (BALB-neuT^664V-E) develop an invasive mammary gland carcinoma by 20 weeks of age. Remarkably, when transgenic BALB-neuT^664V-E mice were vaccinated at a 10- week interval with 50 g 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.