Poliovirus shows promise as a new weapon in the war against brain cancer
Researchers at Duke University show that a polio virus-rhinovirus hybrid may destroy cancer cells in patients with recurrent glioblastoma in phase 1 clinical trials.
You may think of viruses as unthinking, unfeeling agents of disease, but in recent years, researchers have found that with a little tinkering, they can be used in our arsenal of therapeutics to target and kill cancer cells.
Though attempts to use viruses as cancer-destroying agents haven't yet found their place as essential cancer therapeutics, scientists continue to hunt for different ways to utilise them. On Tuesday, researchers at Duke University detailed the results of a phase I clinical trial they've been conducting using PVSRIPO, or modified polio, for the past five years in the New England Journal of Medicine.
In science-speak, PVSRIPO is a "type 1 (Sabin) live-attenuated poliovirus vaccine replicating under control of a heterologous internal ribosomal entry site of human rhinovirus type 2" which essentially means the poliovirus has been genetically modified to be less neurovirulent by fusing it with part of the virus that causes the common cold. That small change means that healthy cells are not susceptible to viral infection.
That small change makes the construct a potential cancer-killer. Naturally, the poliovirus has been shown to infect cells through a specific cell surface receptor known as CD155. In glioblastoma, a type of malignant brain tumour, the CD155 receptor is highly expressed. That makes the tumour cells susceptible to attack by PVSRIPO.
The researchers treated 61 patients with grade IV glioma, who had failed to respond to therapies with PVSRIPO, by delivering it into the tumour through an in-dwelling catheter. After a follow-up time of 27 months, the overall survival among treated patients was similar to that in the historical control group, but after 36 months, 21 percent who received the treatment remained alive.
The scientists vaccinated patients with the polio vaccine prior to installing the catheter and delivering PVSRIPO into the brain tumour. This meant that the body could mount an immune response to the disease, producing the cells necessary to fight back against polio, but also against the cancer.
However, there were some side effects associated with the treatment, with 19 percent of patients having an adverse event of grade 3 or higher, displaying headaches and seizures. There was also one death as a result of the treatment.
In 2016, the US Food and Drug Administration (FDA) designated PVSRIPO a "breakthrough therapy" for glioblastoma, which means it can speed through the FDA review process and receive approval as a treatment option much more quickly than other drugs in development. The results from this phase 1 clinical trial show great promise, but there is still a long way to go before the treatment receives approval. Success in phase 1 trials do not always lead to treatments.
A spokesperson for the National Brain Tumor Society echoed these sentiments, telling CNET "we are encouraged and cautiously optimistic about this innovative approach, which is the result of some really creative science and dedicated efforts by the team at Duke."
"The evaluation of this treatment – and clinical trial process to ultimately determine if the treatment is safe and effective – is still in its very early phases, and there is a lot more data that needs to be seen."
A phase 2 clinical trial, which will determine the efficacy, safety and more clearly expound the side effects of PVSRIPO treatment, is expected to be completed by May 2023.
Carl Zimmer once stated that Earth is an infinity of viruses, outnumbering humans by trillions and trillions, so it's nice to know that in our endless battle against disease, we might be able to call on them for help.
Update, Jun. 28, 4:12 p.m.: Additional comment regarding phase 1 clinical trials, Brain Tumor Society comments
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