Unprecedented T-Cell Immune Responses in Human Trial of DNA Vaccine for Cervical Dysplasia and Cancer Caused by HPV

By Gene Quinn
September 13, 2010

Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that it has achieved best-in-class immune responses in its Phase I dose escalation study of VGX-3100, its DNA vaccine to treat pre-cancerous cervical dysplasias and cervical cancers caused by human papillomavirus (HPV) types 16 and 18. This is a particularly exciting development because HPV types 16 and 18 are responsible for about 70% of cervical cancer incidence.  While success in Phase I is critical, there are substantial hurdles to overcome yet before this vaccine could reach the market.  Nevertheless, such a promising cancer vaccine ought to be heralded by everyone, right?  Think again!  Inovio actually has the audacity to have patents on its ground breaking innovation, which will lead the anti-patent non-thinkers to be more concerned with blowing up the patent system than rooting on Inovio and others as they attempt to eradicate cancer.  Absolutely ridiculous if you ask me!

Lets be perfectly clear, corporations need to make a profit in order for them to stay in existence.  Before a revolutionary biotech or pharmaceutical product can reach the market hundreds of millions of dollars need to be invested, and years, perhaps decades, will go by.  During this black period with no profit these companies rely upon investors to fund potentially game changing innovations.  Together with basic science research in cooperation with Universities — thanks to Bayh-Dole legislation — these companies pursue some of the greatest innovations you and I will ever see, yet they are vilified by those who have built their careers spreading lies about the patent system, science, research and innovation.  Why?  How could anyone do anything other than cheer on those companies who are pursuing cures and treatments for diseases such as cancer?  A good question really.  Clearly the facts, logic and moral argument are on the side of the patent system.  We need more Inovio’s, not less, and we get more by having a first-class patent system that rewards innovators on campus and innovators in the private sector.

Inovio’s VGX-3100 is designed to raise immune responses against the E6 and E7 genes common to HPV types 16 and 18 that are present in both pre-cancerous and cancerous cells transformed by these HPV types. E6 and E7 are oncogenes that play an integral role in transforming HPV-infected cells into cancerous cells. The goal is to stimulate the body’s immune system to mount a T-cell response strong enough to cause the rejection of these infected or transformed cells from the body. The potential of such a vaccine would be to treat cervical cancers, pre-cancerous dysplasias (CINs), as well as persistent HPV infections and other cancers caused by these HPV types.

[Bio-Pharma]

This new generation of vaccines, called DNA vaccine are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. These vaccines, in combination with Inovio’s proprietary electroporation delivery devices, have been shown to be safe and generate significant immune responses. Inovio’s clinical programs include HPV/cervical dysplasia and cancer (therapeutic), avian flu (preventive), and HIV vaccines (both preventive and therapeutic). Inovio is developing universal influenza and other vaccines in collaboration with scientists from the University of Pennsylvania. Other partners and collaborators include Merck, National Cancer Institute, HIV Vaccines Trial Network, National Microbiology Laboratory of the Public Health Agency of Canada, and PATH Malaria Vaccine Initiative.

Overall, in all three doses combined, 13 out of 18 vaccinated subjects (72%) developed significant CTL responses, with positive responses ranging from under 100 to over 5000 SFU per million cells. Fifteen out of 18 vaccinated subjects (83%) developed antibody responses to at least one antigen with most subjects developing responses to two or more antigens.

While the study targeted only safety and immunogenicity as endpoints and did not address clinical efficacy, several literature reports support the hypothesis that induction of tumor antigen specific T-cell responses is important in controlling cancer. Furthermore, there are examples of cancer vaccine candidates targeting the E6 and/or E7 proteins achieving significant clinical efficacy in patients with cervical or vulvar intraepithelial neoplasia, yet the CTL responses achieved in such studies were lower than those observed in the current VGX-3100 study.

Inovio is now planning a randomized, blinded Phase II study of VGX-3100 delivered using its CELLECTRA® intramuscular electroporation device in women with HPV Type 16 or 18 and diagnosed with, but not yet treated for, cervical intraepithelial neoplasia (CIN) 2/3. CIN 2/3s are precancerous lesions that may progress to cervical cancer.

Stanley A. Plotkin, M.D., Emeritus Professor, Wistar Institute and University of Pennsylvania and a member of Inovio’s scientific advisory board, is a vaccine pioneer who developed the rubella and rabies vaccines still being used today. On the news of this exciting step forward by Inovio he said: “Considering that cellular (T-cell) immune responses are known to correlate with suppression of oncogenic transformation (i.e. cell changes that lead to cancer) by HPVs, this study shows the potential for a new therapeutic vaccine to treat cervical dysplasias and cancers caused by those viruses. These are diseases with great unmet medical needs affecting millions of women around the world. The results include some of the best-ever T-cell immune responses induced by a non-replicating vaccine in humans. Therefore, Inovio’s DNA vaccine platform could have significant implications and promise for the advancement of DNA vaccines against cancers and other infectious diseases globally.”

Dr. J. Joseph Kim, Inovio’s President and CEO, said: “We have raised the bar in terms of T-cell immune responses achieved by any DNA vaccine platform in humans. We are pleased that the results of this Phase I study strongly support advancing this vaccine candidate to Phase II clinical studies. An important goal for us was to also validate our DNA vaccine platform in the clinic to support the development of our other vaccine candidates: we have definitively accomplished this goal.”

A tip of the hat to Inovio is in order, as is a tip of the hat to all biotech and pharmaceutical companies that are seeking cures and treatments for those diseases and conditions that are deadly and debilitating.

The Author

Gene Quinn

Gene Quinn is a Patent Attorney and Editor and President & CEO ofIPWatchdog, Inc.. Gene founded IPWatchdog.com in 1999. Gene is also a principal lecturer in the PLI Patent Bar Review Course and Of Counsel to the law firm of Berenato & White, LLC. Gene’s specialty is in the area of strategic patent consulting, patent application drafting and patent prosecution. He consults with attorneys facing peculiar procedural issues at the Patent Office, advises investors and executives on patent law changes and pending litigation matters, and works with start-up businesses throughout the United States and around the world, primarily dealing with software and computer related innovations. is admitted to practice law in New Hampshire, is a Registered Patent Attorney and is also admitted to practice before the United States Court of Appeals for the Federal Circuit. CLICK HERE to send Gene a message.

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  1. One shot wart stop September 14, 2010 12:54 am

    Just to be clear, immunogenicity does not necessarily equate with therapeutic benefits (i.e., the vaccine does not necessarily treat clinical HPV infections). Current studies with Gardasil, which provides significant immunogenicity against the HPV L1 and L2 proteins, not the E6 or E7 “oncogenes,” demonstrate inconclusive therapeutic benefits for Gardasil. I’m not sure anyone is positing that VGX-3100 results in better HPV-based lesion resolution, or that immunogenicity against the E6 and E7 genes (which are almost exclusively intra-celluar) would be uniquely therapeutic. But it would be cool if this is ultimately shown.