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Virus Engineered to Express Melanin Offers New Possibilities to Diagnose and Treat Solid Tumor Cancers

Feb 11 2013 12:00AM

Marketwire

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SAN DIEGO, CA -- (Marketwire) -- 02/11/13 -- In 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 degrees 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.

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