Electrically mediated delivery of vector plasmid DNA elicits an antitumor effect.
In vivo electroporation is an efficient means of increasing plasmid DNA delivery to normal tissues, such as skin and muscle, as well as directly to tumors. In the experiments described here, plasmid DNA was delivered by in vivo electroporation to B16 mouse melanomas using two very different pulsing protocols. Reporter expression increased 21- or 42-fold, respectively with electroporation over injection alone. The growth of experimental melanomas with an approximate diameter of 4 mm on the day of treatment was monitored after electroporation delivery of reporter plasmid DNA. Remarkably, short-term complete regressions using one of these pulsing protocols occurred in up to 100% of mice. These regressions continued long term in up to 83% of animals. 70% of these mice were resistant to challenge with B16 melanoma cells. Histological analysis revealed large numbers of apoptotic cells 24 h after treatment. This antitumor effect did not require therapeutic cDNA expression or eukaryotic sequences.
Heller
L C
LC
Center for Molecular Delivery, c/o Department of Surgery MDC16, University of South Florida, 12901 Bruce B Downs Boulevard, Tampa, FL 33612, USA.
Coppola
D
D
D000818:Animals; D017209:Apoptosis; D018274:Electroporation / Q000379:methods*; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D010957:Plasmids