Polio Virus Being Used to Treat Brain Cancer

According to the results of an early-stage clinical trial published on Tuesday (26/06/2018), a genetically modified polio virus has been used to improve the longer-term survival of patients with a lethal type of brain cancer.

 

21% of patients treated with this virus, all with cancer that had recurred, were alive after three years, compared to just 4% of those who had undergone standard chemotherapy. The trial, that took place recently, involved patients suffering from glioblastoma.
This is a notoriously difficult disease to treat, but it’s one of the most common of all malignant brain tumors. It can cause headaches, blurred vision, confusion, and seizures. Even with aggressive treatment, people who are newly diagnosed rarely survive more than 20 months, while those with a recurrence usually die with a year.

The researchers opened the Phase 1 trial back in 2012 to test the safety of the modified-virus treatment and to try to determine the right dose. After surgeons implanted a catheter in each patient’s brain, a small amount of a genetically modified type of the polio virus was infused directly into the tumor. The virus was designed to target the tumor cells and trigger a response by the immune system. According to the officials, the first participant in the trial was a nursing student who has since gotten married and become a nurse.
Tuesday’s results were welcomed by experts who were not involved in the study. However, these scientists urged caution, saying that it was too early, and the number of patients in the trial too few, to know just how effective the approach is for glioblastoma.
According to the Cancer Institute, while researchers have long viewed such viruses as potential tools for fight cancer cells, they now suspect that the viruses might be more effective at marshaling the body’s immune system against malignancies.
The Duke researchers have said that the median survival for the 61 patients in the trial was 12.5 months, compared with 11.3 months for the “historical control group.” The latter is a group of patients, used for comparison, who were treated earlier with normal chemotherapy and met the criteria for the polio virus trial.
 
A 61-year-old was diagnosed with glioblastoma in 2014 and was treated using surgery, chemo, and radiation. When the cancer returned, she got the polio virus therapy at the cancer institute and went two years without a recurrence.

When the cancer returned, she got a booster infusion of the polio virus late August. She ended up in the hospital with severe side effects. However, now, everything is looking much better.
 
A neurologist who is one of the lead authors of the study, said that the polio virus treatment appears similar to other immunotherapies in that the majority of treated patients don’t respond. However, those who mount “an active immune response” have the real possibility of becoming long-term survivors.

To try to increase the percentage of such responders, scientists opened a Phase 2 trial at the institute and three other medical centers to test the polio virus treatment plus a chemotherapy drug versus only the virus. Researchers are also planning trials for melanoma and breast cancer.

The director of the institute, called the results “very interesting, enough reason to keep going.” However, she noted that it was a very early-phase trial and that the treatment needed more scrutiny.

A neuro-oncologist, called the study “good science” but said the therapy’s effectiveness needed to be tested in a much larger number of patients and at many medical centers.

Both of them questioned the use of a historical control group, rather than an actual one. The director said that it was a “suboptimal way to compare outcomes between patients getting an experimental treatment and those receiving standard therapy.”
The neurooncologist said that the study authors decided a traditional randomized trial would have been unethical because those who didn’t get the treatment would have been subjected to sham procedures, such as insertion of catheters that did not deliver the virus, so that they wouldn’t know whether they were getting the experimental therapy.

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Poliovirus destroys cancer cells and stops tumor regrowth

Researchers  have modified poliovirus to attack cancer tumors. The modified virus appears to unleash the body’s own capacity to fight malignancies by activating an inflammation process that counter’s the ability of cancer cells to evade the immune system.

Their research provides the first insight into the workings of a therapy that has shown promise in early clinical trials in patients with recurrent glioblastoma, a lethal form of brain cancer. The modified poliovirus received a breakthrough therapy designation.

“We have had a general understanding of how the modified poliovirus works, but not the mechanistic details at this level,” said co-senior author  who developed the therapy. “This is hugely important to us. Knowing the steps that occur to generate an immune response will enable us to rationally decide whether and what other therapies make sense in combination with poliovirus to improve patient survival.”
 
The research team elucidated how the poliovirus works not only to attack cancer cells directly, but also to trigger a longer-lasting immune response that appears to inhibit regrowth of the tumor.

Using human melanoma and breast cancer cell lines, and then validating the findings in mouse models, the researchers found that the modified poliovirus therapy starts by attaching to malignant cells, which have an abundance of CD155 protein. The CD155 protein is otherwise known as the poliovirus receptor. The modified virus then begins to attack the tumor cells, directly killing many, but not all. This releases tumor antigens.

The second phase of assault is more complicated. By killing the cancer cells, the modified poliovirus triggers an alarm within the immune system, alerting the body’s defenses to go on the attack.

 Not only is poliovirus killing tumor cells, it is also infecting the antigen-presenting cells, which allows them to function in such a way that they can now raise a T-cell response that can recognize and infiltrate a tumor,” Dr. said. “This is an encouraging finding, because it means the poliovirus stimulates an innate inflammatory response.”

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