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Inovio Therapeutic Hepatitis B Vaccine Killer T Cells Demonstrate Potential to Clear HBV in LiverInovio Advances New Disease Therapy, Where 400 Million Patients Lack Effective Treatment By Inovio Pharmaceuticals, Inc.
Published: Monday, Nov. 12, 2012 - 1:10 am
BLUE BELL, Pa., Nov. 12, 2012 -- /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that its synthetic hepatitis B (HBV) therapeutic vaccine generated strong T cell responses that eliminated targeted liver cells in mice. This data points to the DNA vaccine's potential to clear HBV infection and thereby prevent liver cancer in humans, an encouraging development given that nearly one-third of the world's population is infected with hepatitis B, with 400 million at risk of developing liver cancer.
Results from this preclinical study appear in the peer-reviewed journal, Cancer Gene Therapy, in an article entitled, "Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver."
In the study, Inovio researchers and collaborators constructed a DNA vaccine encoding an HBV core antigen using the SynCon® vaccine technology and administered it via Inovio's proprietary electroporation-based delivery technology. Researchers observed that the vaccine induced strong "killer" T cells in an animal model. Importantly, those killer T cells, while found systemically, were also present in the liver and provided clearance of HBV antigen-expressing liver cells without inducing liver damage.
The company is also investigating additional HBV antigens to develop a multi-component vaccine that can provide the host immune system multiple targets to clear the hepatitis B virus and infected liver cells.
Dr. J. Joseph Kim, Inovio's President and CEO, said, "Inovio has established a potent immune therapeutics platform. With our recent scientific breakthrough represented by our human data showing the powerful killing effect of T cells generated by our cervical dysplasia therapeutic vaccine, we are encouraged by the published preclinical results generated by our therapeutic vaccine against HBV. Hepatitis B is one of the most important global health problems, and we are excited by the prospect of addressing HBV and other chronic infectious diseases with our vaccines.
Scientific Discussion of Results
With a quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, there is a critical need for an effective HBV therapeutic vaccine that can induce strong antigen-specific immune responses and subsequently deploy the immune responses towards the liver.
In this study, Inovio developed a synthetic DNA vaccine which is encoded for the HBcAg antigen and represents a consensus of the unique HBcAg DNA sequences of all major HBV genotypes (A through E). When delivered by electroporation, researchers first demonstrated that this vaccine elicited strong HBcAg-specific T cell and antibody responses in the periphery (outside of the liver) by ELISpot, ICS and cell proliferation assays. Researchers observed that the vaccination could also induce antigen-specific CD8 and CD4 T cells that produced both IFN-y and TNF-a in the liver, indicating a strong vaccine-induced T cell response was also present in the liver.
Furthermore, study researchers found the vaccine-specific T cells exhibited a killing function, and could migrate to and stay in the liver and cause clearance of target cells without any evidence of liver injury. Taken together, this is the first study to provide evidence that intramuscular immunization can induce killer T cells that can migrate to the liver and eliminate target cells.
About Hepatitis B and Liver Cancer
Although an effective preventive vaccine against HBV infection has existed for over three decades, HBV remains a major epidemic, especially among the people of Asian and African descent. One-third of the world's population has been infected with HBV, with 400 million people chronically infected with the virus and at risk of developing cirrhosis or liver cancer. Currently, the only therapies available for chronically infected individuals are interferon-a and nucleoside analog treatments, which function by controlling viral replication but unfortunately do not clear infection. Interferon can prevent viral replication in only 30% of patients and does so with undesirable side effects.
Liver cancer is the third most common cancer and the most deadly, killing most patients within five years of diagnosis. About 600,000 new cases arise each year. One of the major causes and risk factors for liver cancer is infection by hepatitis B.
About Inovio Pharmaceuticals, Inc.
Inovio is revolutionizing vaccines to prevent and treat today's cancers and challenging infectious diseases. Its SynCon® vaccines are designed to provide universal cross-strain protection against known as well as newly emergent unmatched strains of pathogens such as influenza. These synthetic vaccines, in combination with Inovio's proprietary electroporation delivery, have been shown in humans to generate best-in-class immune responses with a favorable safety profile. Inovio's clinical programs include Phase II studies for cervical dysplasia, leukemia and hepatitis C virus and Phase I studies for influenza and HIV. Partners and collaborators include the University of Pennsylvania, Merck, ChronTech, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.
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发表于 2012-11-13 20:15
