Inovio's electroporation tech delivers the goods in trial

Validating the "compelling" preclinical data seen with the MedPulser system in large animal models is a key milestone, said Inovio's chief executive officer, Dr Avtar Dhillon. It suggests that the company's electroporation technology "may provide an important alternative to viral and other DNA delivery technologies and could play a profound role in safely augmenting the immune response generated by future prophylactic and therapeutic immunotherapies against cancers and infectious diseases such as HIV and hepatitis C,"​ he commented. The electroporation process involves applying an electrical current to a tissue or cell, making it easier for active substances to penetrate them. The MedPulser technology opens pores in cell membranes to let in DNA plasmid-based vaccines or other therapies, after which the pores close up again with the drug or vaccine in place. The clinical data are being presented for the first time this week at the 3^rd​ International Conference on DNA Vaccines in Malaga, Spain, by Dr Christian Ottensmeier, Cancer Research UK senior clinical research fellow at the University of Southampton in the UK. Inovio has been collaborating with Dr Ottensmeier since 2005 on the study, entitled 'A Phase I-II Trial of a DNA Vaccine with a PSMA27/pDOM Fusion Gene Given by Intramuscular Injection in HLA2+ Patients with Prostate Carcinomas with or without Electroporation'. So far 24 patients with recurrent prostate cancer have been treated. The study is assessing the safety and tolerability of, as well as cellular (T-cell) and humoral (antibody) immune responses to, the plasmid-based vaccine delivered using electroporation therapy. The vaccine is a proprietary product owned by an unnamed third party. In each arm of the University of Southampton study (i.e., with and without electroporation delivery), three patient groups are being treated with escalating dosage levels of the vaccine. An analysis of interim data from the first- and (partially) the second-dose treatment groups showed that electroporation appeared to be safe and was well tolerated. Moreover, there were signs of efficacy with patients showing significant antibody responses numbering four out of 10 in the patient groups treated without electroporation and nine out of 10 in the groups treated with electroporation. The magnitude of the antibody response was significantly higher in the patients treated using electroporation, said Inovio. Data on T-cell responses are being compiled and the investigators continue to enrol (target: 30 patients) and treat patients in the higher-dosage groups, Inovio added. "These data demonstrate for the first time in a clinical trial that the significant enhancement in potency of a gene-based vaccine delivered by electroporation in animals can also be seen in humans,"​ Dr Ottensmeier said. DNA plasmids are designed to express antigens that can induce an immune response specific to a cancer or infectious disease-causing organism, Inovio noted. The plasmids are created synthetically and are readily manufactured using well-established bacterial fermentation and purification techniques. Three other Phase I programmes are underway using the MedPulser electroporation technology. They involve interleukin-12 delivered directly to malignant melanomas, in collaboration with RMR and the H Lee Moffitt Cancer Center and Research Institute; interleukin-2 delivered directly to malignant melanomas (with Vical); and a DNA vaccine delivered intramuscularly for breast, ovarian and colorectal cancers expressing HER2 and/or carcinoembryonic antigen (Merck & Co).