Duke researchers in the US use the modified virus to spur natural immune attack against tumours in animal studies
A modified form of poliovirus, pioneered at Duke Cancer Institute as a therapy for glioblastoma brain tumours, appears in laboratory studies to also have applicability for paediatric brain tumours 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) tumours.
The cancer strikes children and is universally deadly.
Reporting this week in the journal Nature Communications, the researchers described how a polio-rhinovirus chimera (PVSRIPO), modified to express a mutate tumour antigen found in DMG, is able to infect and induce the activity of dendritic cells.
Dendritic cells prime tumour antigen-specific T-cells to migrate to the tumour site, attack tumour cells, delay tumour growth and enhance survival in animal tumour 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 Matthias Gromeier, M.D., who developed the poliovirus-based therapy as a member of Duke’s Preston Robert Tisch Brain Tumour 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.”
Gromeier 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 tumours, which exact a terrible burden on children and their families,” Gromeier said.
Source: Duke University Medical Center