First Human Demonstration Of Significant, Persistent Antibody Response Using Electroporation-Delivered DNA Vaccine Published In Human Gene Therapy

Main Category: Genetics
Also Included In: Immune System / Vaccines
Article Date: 05 Aug 2009 - 15:00 PDT

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Inovio Biomedical Corporation (NYSE Amex: INO), a leader in DNA vaccine design, development and delivery, announced today new data representing what Inovio believes to be the first demonstration of a significantly increased and persistent level of antibody response generated by a DNA vaccine delivered using electroporation.

The results, generated in a clinical study conducted by Inovio's collaborators, the University of Southampton and The Institute of Cancer Research in the U.K., were published in the medical journal Human Gene Therapy, July 20, 2009, in a paper entitled, "DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer." The DNA vaccine is designed to induce a strong helper T-cell response, with the aim of enhancing induction of a cytotoxic T-cell response against tumor cells. Measuring antibody (humoral) responses against the helper sequence in the vaccine may help judge the vaccine's potential performance. It may also allow predictions of vaccine performance in other settings, for example, against viral and bacterial diseases, where strong antibody responses are imperative in providing protection.

This open label phase I/II, two arm, dose escalation trial is evaluating a novel DNA vaccine based on a prostate specific membrane antigen (PSMA) fused to a tetanus toxin (DOM). The PSMA antigen is designed to induce a CD8+ T-cell response capable of killing tumor cells; the DOM element is designed to help enhance the immune response to PSMA. The study is also evaluating delivery of this DNA vaccine with and without Inovio's proprietary electroporation delivery technology. In each arm, five patients were treated at each of three dose levels. The protocol included three vaccinations at four week intervals followed by booster doses at 24 and 48 weeks.

The published data completes the reporting of antibody responses in the 30 patients vaccinated in this study. The data indicate that the use of electroporation yielded significantly enhanced antibody responses to DOM while the absence of electroporation resulted in low anti-DOM antibody responses (25-fold mean increase over baseline compared to a 1.5-fold mean increase, respectively). Importantly, the level of antibody response further increased following additional boosts of DNA vaccine delivery via electroporation at later time points. Furthermore, antibody responses persisted out to 18 months of follow-up, a significant result that would be useful in the context of a practical vaccine regimen. As reported in prior releases, this vaccine was found to be safe and well tolerated. Analyses of T-cell immune responses to the PSMA antigen are ongoing.

Dr. Christian Ottensmeier of the University of Southampton, principal investigator on the study, commented, "We are pleased to publish these data indicating a notably higher induction of antibodies to the tetanus toxoid component upon DNA vaccination with electroporation. The antibody levels appear to be in a range comparable to traditional protein-based vaccination or injection of attenuated or inactivated pathogen. With the advantageous safety profile of electroporation-delivered DNA plasmids indicated by human data to date, this data supports optimism for use of this next-generation vaccine modality as a strategy against infections and cancer."

Dr. J. Joseph Kim, Inovio's CEO, said, "We have demonstrated in different human trials that Inovio's electroporation devices are safe and well-tolerated. This longer-duration data further validates the importance of our electroporation technology in achieving the primary goal of scientists in this field, which is to improve the immunogenicity of DNA vaccines in humans. These results bode well for our programs in development."

The development of this DNA vaccine was supported by the UK cancer charities the Leukemia Research Fund and, Cancer Research UK and rights to the vaccine are owned by Cancer Research Technology Limited. The study was supported by Cancer Research UK funding, the Allan Willett Foundation, Inovio Biomedical Corporation, and the Experimental Cancer Medicine Centre in Southampton. The clinical study is a collaborative project between the University of Southampton with Southampton University Hospitals NHS Trust and the Institute of Cancer Research with the Royal Marsden NHS Foundation Trust, Sutton, Surrey.

Source
Inovio Biomedical Corporation

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