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Using a poliovirus vector to head off cancer
DURHAM, N.C.—The effort to fight tumors with vaccines continues, and this time with one of the hardest to treat: brain cancer, with Duke University researchers announcing recently that a modified form of poliovirus, pioneered at the Duke Cancer Institute as a therapy for glioblastoma brain tumors, appears in laboratory studies to also have applicability for pediatric brain tumors when used as part of a cancer vaccine.
Working with mouse models and human cancer cells, the Duke team found that an injection of the modified poliovirus vector set off immune system activity that zeroed in on that mutated cancer cells that predominate in diffuse midline glioma (DMG) tumors. The results were published in the journal Nature Communications under the title “Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.”
They described how a polio-rhinovirus chimera (PVSRIPO), modified to express a mutate tumor antigen found in DMG, is able to infect and induce the activity of dendritic cells (DCs). DCs prime tumor antigen-specific T cells to migrate to the tumor site, attack tumor cells, delay tumor growth and enhance survival in animal tumor models. But their activity can be difficult to control.
“Polioviruses have several advantages for generating antigen-specific CD8 T cells as a potential cancer vaccine vector,” said senior author Dr. Matthias Gromeier, a professor in the departments of Neurosurgery, Molecular Genetics and Microbiology and Medicine at Duke. Gromeier developed the poliovirus-based therapy as a member of Duke’s Preston Robert Tisch Brain Tumor Center. “They have naturally evolved to have a relationship with the human immune system, activating dendritic cells, inducing CD8 T cell immunity and eliciting inflammation. As a result, they lack interference with innate or adaptive immunity.”
As the authors note in the paper, “Failure of early cancer vaccines—usually short peptides—were attributed to lacking DC engagement. Above all, peptide vaccination without proper DC costimulation and proinflammatory cytokines can induce tolerance or T cell anergy. We show that pharmacokinetic problems of peptide vaccination, e.g. poor uptake/presentation by DCs, are resolved with PVSRIPO vectors.”
Gromeier and his team are continuing to test the vaccine approach, with an eye toward eventually starting a Phase 1 clinical trial.