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We report successful electro-gene therapy (EGT) by using plasmid DNA for tumor-bearing mice. Subcutaneously inoculated CT26 tumor was subjected to EGT, which consists of intratumoral injection of a naked plasmid encoding a marker gene or a therapeutic gene, followed by in vivo electroporation (EP). When this treatment modality is carried out with the plasmid DNA for the green fluorescent protein gene, followed by in vivo EP with the optimized pulse parameters, numerous intensely bright green fluorescent signals appeared within the tumor. EGT, by using the ''A'' fragment of the diphtheria toxin gene significantly inhibited the growth of tumors, by about 30%, on the flank of mice. With the herpes simplex virus thymidine kinase gene, followed by systemic injection of ganciclovir, EGT was far more effective in retarding tumor growth, varying between 50% and 90%, compared with the other controls. Based on these results, it appears that EGT can be used successfully for treating murine solid tumors.

Electroporation can deliver exogenous molecules like drugs and genes into cells by pulsed electric fields through a temporary increase in cell membrane permeability. This effect is being used for the treatment of cancer by intratumoral injection of low dosage of an otherwise marginally effective chemotherapeutic drug, bleomycin. Application of a pulsed electric field results in substantially higher uptake of the drug and enhanced killing of the cancer cells than is possible by conventional methods. The MedPulser, a new treatment system for local electroporation therapy (EPT) of head and neck tumors was developed and is described in this paper. EPT with bleomycin has been found to be very effective in killing cancer cells in vitro, in mouse tumor xenografts in vivo, and in tumors in humans. Ten head and neck cancer patients with recurring or unresponsive tumors were enrolled in a Phase I/II clinical trial. Treatment of the entire tumor mass in each of eight patients resulted in five complete responses confirmed by biopsy and MRI, and three partial responses (> or = 50% shrinkage). Two additional patients who received partial treatment of their tumor mass had local response where treated, but no overall lesion remission. Duration of the complete responses ranges from 2-10 months to date. All patients tolerated the treatment well with no significant local or systemic adverse effects.

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