Efficient DNA electrotransfer into tumors

DNA transfer to tumor cells of antiproliferative genes or of genes coding f or immunomodulatory or antiangiogenic products is a promising approach for cancer therapy. However, intratumoral injection of plasmid DNA either naked or associated to chemical vectors results in a low level of gene expressio n. Recently, electrically mediated gene transfer has been described to stro ngly increase foreign gene expression in various tissues. We confirm and ex tend these observations using long duration electric pulses for several mur ine and human tumor models, using a reporter gene encoding for luciferase. After plasmid intratumoral injection, eight electric pulses of 20-ms durati on were delivered at a frequency of 1 Hz through two flat parallel stainles s steel electrodes placed at each side of the tumor. Optimal gene transfer was obtained using a voltage-to-distance ratio comprising between 400 and 6 00 V/cm. Two days after electrotransfer, we obtained a 10- to 1200-fold inc rease in gene expression over the naked DNA injection alone, leading to the expression of 0.6 to 300 ng luciferase per tumor. Moreover, histological r esults using beta -Gal reporter gene injected in H1299 tumor indicate that electrotransfer leads to a substantial increase in the percentage of beta - Gal positive cells. These results confirm the wide potential of electrotran sfer for gene therapy in cancer. (C) 2000 Elsevier Science S.A. All rights reserved.