Research in cell cultures and animal models suggests that scientists may be able to use a modified poliovirus to mount an immune response against brain tumor cells.
Scientists know that the poliovirus is the pathogen that causes poliomyelitis, a disease that affects the central nervous system, potentially causing disability and, in the most severe cases, death.
But, increasingly, researchers have found that they can modify existing viruses to make them safe and, most importantly, harness their potential in challenging and fighting other health conditions.
Recently, a team of investigators from the Duke Cancer Institute in Durham, NC, has discovered that they might be able to use the poliovirus in the treatment of a form of brain cancer.
In their study paper — which appears in Nature Communications — the researchers explain that they have genetically modified the virus, creating a stable, safe version called a “chimera.”
This modified version, they say, can boost the immune response against diffuse midline glioma — a type of extremely aggressive brain tumor — that is more common in children than adults.
The research so far has been preclinical, which scientists have conducted in vitro, in cancer cells they have collected from humans, and in vivo, in mouse models.
For their study, the investigators modified a polio-rhinovirus chimera to get it to express a mutated tumor antigen that is usually present in diffuse midline glioma.
Antigens are structures that stimulate an immune system response, and, in the current case, the mutated antigen stimulates the activity of dendritic cells. In turn, dendritic cells spur into action a group of specialized immune cells called “tumor antigen-specific T cells.”
Such T cells can lock in on tumors and start killing the cancer cells that form them, thus delaying tumor growth and prolonging survival.
However, in previous experiments, these immune cells have also proved very difficult to control, as they mistakenly also attacked healthy tissue.
This is where the modified poliovirus appears useful, according to the study authors.
“Polioviruses have several advantages for generating antigen-specific CD8 T-cells as a potential cancer vaccine vector,” explains senior author Dr. Matthias Gromeier.
The virus, the researcher notes, is able to activate dendritic cells and stimulate an immune response against “the invader” — cancer — without threatening other aspects of health.
“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,” says Dr. Gromeier.
Thus, the newly created version of the poliovirus could potentially act as a “vaccine” against aggressive brain tumors.
So far, the experiments in cells and mouse models have shown enough promise to lead the researchers to plan a phase 1 clinical trial, involving human participants.
“We are hopeful that this approach could be tested as a potential therapy for [diffuse midline glioma] tumors, which exact a terrible burden on children and their families.”
– Dr. Matthias Gromeier