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The Importance of Imaging

The Importance of Imaging ARTICLE EXTRAS To Build a Killing Machine A selected list of oncolytic viruses in clinical trials Moments after being injected with a tagged virus, the entire body of a mouse glows under specialized cameras designed to pick up light emanating from deep beneath the skin. Over time the light becomes concentrated to a few key spots. These are the tumors where the virus, a strain of vaccinia, is replicating

Andrew Holtz

The Importance of Imaging



Moments after being injected with a tagged virus, the entire body of a mouse glows under specialized cameras designed to pick up light emanating from deep beneath the skin. Over time the light becomes concentrated to a few key spots. These are the tumors where the virus, a strain of vaccinia, is replicating like mad.

"That's what we like to see: strong signal in the tumor and not much anywhere else," says virologist Steve Thorne, a research associate at Stanford University. Thorne collaborates with David Kirn, who founded Jennerex on the premise that engineered vaccinia virus can be employed as a cancer-killing tool.

Thorne was at his grandfather's funeral outside of London when he first heard about the American scientist who was looking to develop viruses to selectively infect and...

"My grandfather was David Kirn's cousin's godfather," Thorne says. Kirn had recently arrived at Imperial College London after leaving Onyx Pharmaceuticals in San Francisco. Though he knew little about oncology, Thorne sent Kirn a resume and soon joined him at Imperial College as a postdoc in 2001. When Kirn returned to the Bay Area to start a company on the work they had done, he beckoned Thorne to follow. Thorne now works with Christopher Contag at Stanford, who pioneered technologies for imaging infections and cell types in living mammals.

By engineering bioluminescent proteins such as luciferase into the vaccinia viruses being designed for cancer therapy, Thorne has been able to follow the spread of infections in mouse models of cancer.

Recently Thorne along with Contag and Robert Negrin tracked vaccinia replication in mice injected with vaccinia alone or with vaccinia infected T cells. By preinfecting so-called cytokine-induced killer cells (CIK), they were able to show a synergistic effect against tumors in the animals (S.H. Thorne et al., Science, 311:1780-4, 2006).

While the cameras work well with tiny animals, they can't see deeply enough to be useful in people. But for research purposes, they're invaluable. "To do these experiments without imaging, we'd have to sacrifice lots of animals at lots of different time-points and laboriously grind up all the tissues within the animals separately ... This way, we can come back and image the same animals at different times and get a much clearer idea of where the virus is," Thorne says.

Kirn says that compared to traditional measures of tumor size or biopsies of tumor cells, these images are both better and faster. "It shows you the biology of what's happening, rather than just a crude tumor measurement, for example. Certainly, we look at that as well, but this tells you the biology behind it ... and the more you understand it, the more you can tweak the system to improve it."

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