A modified poliovirus may be an important new weapon in combating a host of cancers. An investigational therapy using modified poliovirus to attack cancer appears to unleash the body’s own capacity to fight malignancies by activating a newly identified inflammatory process.
In an article published in the journal Science Translational Medicine, researchers at Duke Cancer Institute report on a therapy that has shown promise in early clinical trials in patients with recurrent glioblastoma. The modified poliovirus received a breakthrough therapy designation from the U.S. Food and Drug Administration last year.
The current investigation explores the adjuvant therapy and cancer immunotherapy potential of the recombinant poliovirus/rhinovirus chimera PVSRIPO. Currently, PVSRIPO is in clinical trials for the treatment of recurrent World Health Organization grade IV malignant glioma. Researchers report that PVSRIPO causes cytopathogenic infection of neoplastic cells to release the proteome. It also exposes pathogen-associated molecular patterns and damage-associated molecular patterns.
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 poliovirus receptor). The modified virus then begins to attack the tumor cells, directly killing many, but not all, which then releases tumor antigens.
“We identified an unusual relationship of our investigational agent, PVSRIPO, with antigen presenting cells (dendritic cells, macrophages), indicating that PVSRIPO infection of tumors may have unique potential for inducing tumor antigen-specific antitumor immunity. We had vague signs of such a relationship early on, but the true extent of the inflammatory and immunogenic effects of PVSRIPO infection of myeloid cells was a surprise,” said co-senior study author Matthias Gromeier, MD, a professor in the Duke Department of Neurosurgery in Durham, North Carolina.
He said his team had a general understanding of how the modified poliovirus worked. However, these new findings may have significant clinical implications. Knowing the steps that occur to generate the observed immune response could pave the way for tailored combination therapies with poliovirus.
“Immune checkpoint inhibitors have shown unprecedented promise in those cancers with underlying, pre-existing antitumor immunity. These agents can very effectively unmask such pre-existing responses,” Dr. Gromeier told OncoTherapy Network. “To extend this promise to the vast majority of cancers, which are less ‘immunogenic’, or to patients who failed/developed resistance to checkpoint inhibitor therapy, approaches that can initiate new antitumor immune repertoires are needed.”
He said there is broad agreement in the field that the most efficacious means to achieve this goal is to engage innate antiviral responses in antigen-presenting cells. The current investigation suggests it may be possible with PVSRIPO. “We have identified new mechanisms to generate tumor antigen-specific antitumor immunity with an oncolytic poliovirus recombinant. This is the eminent goal of cancer immunotherapy,” said Dr. Gromeier.