How poliovirus unleashes an attack on glioblastoma

glioblastoma
A modified form of poliovirus may prompt the immune system to seek out and destroy glioblastoma tumors.

In 2015, a team of researchers at Duke University was launched into the spotlight by CBS news show 60 Minutes, which devoted a two-part segment to research aimed at turning poliovirus into a treatment for the aggressive brain cancer glioblastoma. Only a handful of patients had received the experimental therapy at the time, and it wasn’t clear if the virus would pan out as a cancer treatment.

Now that same team has released a study that delves into the process by which the virus fights malignancy. It appears to do so by activating an inflammatory process, the researchers believe. That inflammation interferes with the ability of cancer cells to escape immune attack, according to a press release. The research was published in the journal Science Translational Medicine.

The modified poliovirus the team is developing, which has been engineered to preferentially seek out and destroy cancer cells, works by attaching to a protein on the surface of malignant cells called CD155. The virus directly kills some glioblastoma cells, thereby triggering an “alarm” in the immune system, the researchers said. That step seems to occur when the virus infects dendritic cells and macrophages. This unveils the brain tumor, making its cells vulnerable to an ongoing attack by the immune system.

"We have had a general understanding of how the modified poliovirus works, but not the mechanistic details at this level," said co-senior author and Duke neurosurgery professor Matthias Gromeier, M.D., in the statement. "Knowing the steps that occur to generate an immune response will enable us to rationally decide whether and what other therapies make sense in combination with poliovirus to improve patient survival."

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In fact, combining modified viruses with other immune-boosting treatments is an idea that’s gaining steam in oncology. Amgen’s Imlygic, a modified form of herpes virus and the first such “oncolytic virus” to gain FDA approval, is approved as a solo therapy for melanoma but is now in clinical trials in combination with Merck’s Keytruda. The Merck product takes a different approach to stimulating the immune system by inhibiting PD-1, a “checkpoint” protein that normally prevents it from recognizing and attacking tumor cells.

Several other viruses are being studied for their anticancer effects, including Zika, which may also prove useful against brain cancer. Earlier this month, scientists at Washington University School of Medicine in St. Louis and the University of California at San Diego announced that when they injected mouse models of aggressive glioma with a modified form of Zika, the virus slowed the growth of brain tumors and extended the animals’ lives.

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Gromeier and three members of his team at Duke have patented their poliovirus-based treatment and licensed it to a company he co-founded, Istari Oncology. Future studies aim to uncover more details about how the immune system’s activity changes after it is exposed to the modified poliovirus.