DNA immunization using constant-current electroporation affords long-term protection from autochthonous mammary carcinomas in cancer-prone transgenic mice.
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 microg 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 microg 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.
Curcio
C
C
Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Khan
A S
AS
Amici
A
A
Spadaro
M
M
Quaglino
E
E
Cavallo
F
F
Forni
G
G
Draghia-Akli
R
R
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018274:Electroporation; D005260:Female; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods*; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D010957:Plasmids; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D019496:Cancer Vaccines; D006023:Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C483804:Erbb2 protein, rat