A modified form of poliovirus, 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.
In preclinical studies using mice and human cancer cells, an injection of the modified poliovirus vector instigated an immune response that homed in on mutated cancer cells that predominate in diffuse midline glioma (DMG) tumors. The cancer strikes children and is universally deadly.
Reporting in the journal Nature Communications, the researchers 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.
Dendritic cells 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.
"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."
The authors show that the dendritic cells efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models.
The author said the vaccine approach continues to be tested with the goal of initiating a phase 1 clinical trial.
"We are hopeful that this approach could be tested as a potential therapy for DMG tumors, which exact a terrible burden on children and their families," the author said.
Poliovirus therapy shows potential as brain cancer vaccine in lab studies
- 442 views