SAN DIEGO, 11 Feb. 2013In a study released today in Proceedings of the National Academy of Sciences (PNAS), entitled Vaccinia virus mediated melanin production allows MR and optoacoustic deep tissue imaging and laser induced thermotherapy of cancer, scientists combined the natural imaging potential of melanin with recombinant Vaccinia viruses ability to selectively enter and replicate within tumor cells. Melanins, dark pigments found in most organisms, are produced in certain types of cancers, such as melanoma, causing tissues to appear very bright in Magnetic Resonance Imaging (MRI). Significantly, the approach achieved sufficient concentrations of melanin in tumor cells to enable enhanced MRI and optoacoustic imaging (using sound and light waves to detect masses), as well as thermotherapy (laser-induced thermal lysis) of melanin-producing tumor cells.
At Genelux, we have been working to develop new recombinant vaccinia virus strains suitable for deep tissue imaging, such as PET and MRI, said Jochen Stritzker, Ph.D., the study’s first author and Associate Vice President for Molecular and Clinical Imaging at Genelux Corporation. In this study we were able to show for the first time, that the virus-mediated production of melanin has many benefits and may be used as a visible marker during surgery, a mediator of laser-induced thermotherapy, and a reporter, (an easily identified and measurable gene product) when expressed in cells for MRI and optoacoustic imaging.
To facilitate melanin production, researchers inserted the genetic information encoding melanin-producing enzymes into the viral genome of engineered vaccinia virus strains that infect cancer cells. Such virus infection (colonization) created high concentrations of melanin within the virus-infected tumor cells of live mice. In fact, the concentrations were so high that tumors isolated from mice appeared coal black in color. Moreover, MRI effectively detected this virus-mediated melanin production and localization in solid tumors and also in very small metastases.
Such novel production of imaging and therapeutic agents became feasible because of the large foreign-gene-carrying capacity and efficient tumor colonization by the vaccinia virus, which only replicates in the cell’s cytoplasm, said Aladar Szalay, Ph.D., senior study author and Founder and CEO of Genelux Corporation. Moreover, these experiments open a new field of rational design and production of imaging agents without the need for added substrates which currently limit the use of most imaging agents.
Scientists also used near infrared lasers to significantly increase the temperature of the light-absorbing, melanin-producing tumor cells and tissues to a temperature of more than 150°F. The presence of melanin in tumor cells resulted in effective thermotherapy, as the temperature increase was sufficient to effectively destroy the melanin-producing tumor cells in live animals. In comparison, healthy non-melanin producing cells allowed little light absorption, could only be heated by a few degrees, and no cell death was observed.
The study also found new melanin-encoding viral strains to be effective for generation of specific signals in Multispectral Optoacoustic Tomography (MSOT), a novel technology for high-resolution molecular imaging deep inside tissues to generate a 3-D image of the site(s) of greatest light absorption. Since light absorption by brownish-black melanin is very high, the study found MSOT signals to be very intense in virus colonized, melanin producing tumors and metastases allowing excellent imaging.
Using melanin producing enzymes as reporters will not only have a significant impact on basic research, for example, in aiding visualization of stem cells in animal models, said William G. Bradley, M.D., Ph.D., FACR, chair of the Department of Radiology at the University of California, San Diego (UCSD) School of Medicine and study co-author. It is likely also to be used in medical applications, beginning with melanin producing viruses tested in clinical trials in human cancer patients. One day we may see laser-mediated thermal ablation of melanin producing tissues when surgical removal is not an option.
About Genelux Corporation
Headquartered in San Diego, California, Genelux Corporation is a privately held, clinical stage biopharmaceutical company dedicated to fundamentally changing the way in which cancer is diagnosed and treated. The company has developed a proprietary oncolytic vaccinia virus-based technology platform that can be engineered to insert specific therapeutic genes for delivery and amplification of anti-cancer proteins and RNA into cancer cells without harming healthy cells. This platform includes a green fluorescent protein (GFP) as a bioluminescent diagnostic. The company is also incorporating advanced diagnostic deep-tissue imaging technologies into its viral platform to enable highly specific visualization of tumors and circulating cancer cells. GL-ONC1, the company’s lead oncology product candidate, is an attenuated vaccinia virus (Lister strain) that is currently under evaluation in multiple human clinical trials in the US and Europe. For more information please visit http://www.genelux.com.
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