Poliovirus therapy induces immune responses against cancer

An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells to evade the immune system. 

Duke Cancer Institute researchers provide the first published insight into the workings of a therapy that has shown promise in early clinical trials in patients with recurrent glioblastoma, a lethal form of brain cancer. The modified poliovirus received a breakthrough therapy designation from the Food and Drug Administration last year, expediting research.

"We have had a general understanding of how the modified poliovirus works, but not the mechanistic details at this level," said co-senior author Matthias Gromeier, a professor in the Duke Department of Neurosurgery who developed the therapy. "This is hugely important to us. 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."

The research team elucidated how the poliovirus works not only to attack cancer cells directly, but also to trigger a longer-lasting immune response that appears to inhibit regrowth of the tumor.

Using human melanoma and breast cancer cell lines, and then validating the findings in mouse models, the researchers found that the modified poliovirus therapy starts by attaching to malignant cells, which have an abundance of CD155 protein. The CD155 protein is otherwise known as the poliovirus receptor. The modified virus then begins to attack the tumor cells, directly killing many, but not all. This releases tumor antigens.