Genetically Engineered Poliovirus Fights Brain Tumors

"Malignant glioma (the most common type of brain tumor) is almost always fatal, due to very poor response to surgery, radiation and chemotherapy," says Matthias Gromeier, in whose laboratory the research was conducted. "We have developed a new form of therapy against malignant glioma based on viruses that can cause brain infections in humans."

The creation of this new therapy began when Gromeier and his colleagues discovered that the molecule that the poliovirus binds to on human cells, CD155, is abnormally expressed on malignant gliomas. This meant that the poliovirus would naturally target brain tumors. Unfortunately, the use of the virus as a treatment was severely limited by its ability to cause polio in humans.

"We genetically engineered a poliovirus variant that lost its ability to cause disease in humans. We accomplished this task by inserting a piece of genetic information of rhinovirus (the virus that causes the common cold) into the poliovirus genome," says Gromeier. "The mixed polio/rhinovirus construct had very surprising properties: it had lost its ability to cause poliomyelitis in humans, but retained excellent killing potential for malignant glioma cells."

They tested the abilities of this new hybrid virus using mice with experimental brain tumors. The animals recovered after a single dose of the virus. "Pathological analysis of their brains revealed tumors to be eliminated by replicating virus within days," says Gromeier.

This research was conducted with support from the American Cancer Society, the National Cancer Institute and the Burroughs Wellcome Fund.