Poliovirus slaughters brain tumors in mice

Scientists have harnessed the killing power of a debilitating virus to slay

even more deadly foes–malignant brain tumors. In research on mice, Mattias M. Gromeier and his colleagues altered a live poliovirus, inducing it to attack and eliminate tumor cells in the animals’ brains.

The modification changes the virus just enough so that it can’t cause polio. “We are not trying to coerce the virus into doing something it is not fit or designed to do, but rather exploit the natural ability of this remarkable pathogen to target and destroy certain cell types,” says Gromeier, a microbiologist at Duke University in Durham, N.C. He presented the research results in Orlando, Fla., this week at the meeting of the American Society for Microbiology.

According to the American Brain Tumor Association, 180,000 people will be diagnosed with brain tumors in 2001. The traditional cancer-fighting therapies–radiation, surgery, and chemotherapy–remain woefully inadequate for most brain tumors, says Philip H. Gutin, chief of neurosurgery of Memorial Sloan Kettering Institute in New York. By the time physicians detect a brain tumor, it has usually spread and damaged critical areas of the organ.

The most common brain tumors, malignant gliomas, “are all absolutely fatal,” says Gutin, who has worked with Gromeier.

Even balanced against that grim prospect, poliovirus seems an unlikely savior. Polio has claimed hundreds of thousands of victims worldwide. The virus selectively attacks motor neurons, the nerve cells that control movement, and thus kills its victims or causes permanent, partial paralysis.

However, it’s poliovirus’ unique specificity for motor neurons that makes it the perfect vehicle for killing tumor cells in the brain, says Gromeier. The virus can get into cells only one way. It uses CD155 binding protein, a molecule on the surface of motor neurons, as its key to get inside.

Moreover, the virus only reproduces in and kills motor neurons. Once inside the cell, viral genes recognize the motor neuron and start the copying process. The resulting excess of viral particles kills the cell.

Although in a healthy body, no cells other than motor neurons make CD155, tumor cells in the brain produce large quantities of the molecule. The substance provides a handy beacon for poliovirus.

However, once inside the tumor cell, the unaltered virus wouldn’t reproduce, and the cell would remain alive.

The researchers replaced the segment of the poliovirus genome that recognizes the interior of a motor neuron and starts replication. They inserted a similar segment from rhinovirus, a virus that causes the common cold and can reproduce in a variety of cells.

The altered poliovirus could invade both tumor cells and motor neurons, but it replicated only in the tumor cells.

When the team injected the altered poliovirus into large malignant gliomas in mice, the tumors disappeared within days or weeks. None of the mice contracted polio.

Other researchers have similarly modified herpes virus and another cold virus to battle brain tumors (SN: 8/19/00, p. 128), but these viruses are less specific because they attach to many different surface molecules.

The new study is exciting, says Casey Morrow of the University of Alabama at Birmingham, because CD155 could specifically bind altered poliovirus to many types of brain tumors.

It’s hard to know whether patients would shy away from being injected with a live poliovirus, says Gutin. “People with brain tumors are so desperate, I don’t think that when you’re dying of brain cancer the prospect of getting polio is too off-putting,” he says.

The researchers haven’t yet gained approval from the Food and Drug Administration for a trial of the new therapy in people. Even if they do, Gromeier says, actual therapy with altered poliovirus would be years away.

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