From using CRISPR to immune-stimulating agents, biomedical science has even got as far as not just killing off cancerous cells, but coming up with vaccines for them. These are, for the most part, carried out on animal subjects, though – a necessary safety and efficacy-checking step on the path to clinical use in humans.
That’s why a new study, published in the New England Journal of Medicine, is so exciting: a new type of life-prolonging treatment for brain cancer seems to have taken hold in some human patients – and it relies on the use of the oft-dangerous poliovirus, something we’ve almost entirely eradicated.
The treatment, spearheaded by the Duke Cancer Institute in Durham, North Carolina, targeted glioblastoma, a particularly deadly form of brain cancer. From 2012 to 2017, 61 patients who had a particularly grim prognosis for their glioblastoma were given the treatment through a catheter surgically implanted in their skulls.
Half were still alive after just over 12 months, compared to 11.3 months for other patients that historically received conventional treatments. After 24 months, 21 percent of those given the new treatment were alive, compared to just 14 percent in the control group.
That 21 percent held over 36 months, while the control group dropped to 4 percent. Two of the patients were still alive at 69 months.
As the authors of the study note, “there is currently no effective therapy” for glioblastoma. Could this treatment be the answer? Perhaps, but it’s very early days.
This was a Phase I trial, one designed to see if the dose given during the treatment was safe or not. It had a small sample size, and results varied somewhat erratically between patients.
The treatment was ineffective for most, though, and as noted by Reuters, most patients experienced some sort of negative side effect.
Some patients on a higher dose experienced brain swelling and seizures, so the dose was adjusted. One patient, after the catheter was removed, suffered from a “grade 4 intracranial hemorrhage”, something that required emergency surgery to fix.
Despite all this, the results are promising. So how does the treatment use the poliovirus to work?
Viruses are rather good at destroying various cells by injecting them with their genetic material and ultimately causing new viruses to burst forth from their living shell.
Found both in nature and designed in the laboratory, oncolytic – cancer-killing – viruses exist too. Anti-cancer viral therapy isn’t hypothetical, it really exists: Already, a genetically modified form of the herpes virus has been approved by the US Food and Drug Administration for clinical use in patients with skin cancer.
As noted by the National Cancer Institute, the way in which oncolytic viruses actually work is still uncertain. They may be directly destroying the cancerous cells themselves, but research is beginning to show that they can also trigger an immune response that does the work for them.
The general idea is that when the virus infects, replicates within, and annihilates the cell, it also releases compounds, including toxic components of the tumor, which allows the cancer to be identified by the immune system.
That’s what’s thought to have been happening in the latest trial. The poliovirus was tweaked to render it unable to cause polio; it had the relevant gene replaced by one from a harmless rhinovirus, which made the final product a “polio–rhinovirus chimera” or PVSRIPO.
Driven by the poliovirus part, the chimera infected the patients’ immune systems, as per usual. As it did so, it infected the cancerous cells in their brains, which seemed to trigger the body’s own immune system to sweep the decks.
Exciting times, yes – but as ever, plenty more research is required before we can say whether this is the silver bullet for glioblastoma or not.