Story highlights Poliovirus can attach to a receptor found on the surface of almost all solid tumor cancer cells Researchers engineered a safe version of the poliovirus to inject into tumors (CNN) — There’s a surprising upside to the virus that causes polio disease, new research indicates. An engineered version of poliovirus improved the overall survival rate of patients with a lethal form of brain cancer, according to results from a phase one clinical trial. Among 61 patients with recurrent glioblastoma who received the experimental therapy, 21% will survive for three years or longer, compared with just 4% of patients treated with multiple sessions of chemotherapy, the current standard therapy. “This is only the first step, and it’s opening the door to multiple new trials,” said Dr. Matthias Gromeier, a co-author of the study and a professor of neurosurgery at the Duke University School of Medicine. In the next few weeks, the researchers will begin clinical trials on patients with melanoma skin cancer and breast cancer, explained Dr. Darell D. Bigner, a co-author of the study, a professor of pathology and emeritus director of The Preston Robert Tisch Brain Tumor Center at Duke University. “We are encouraged and eager to continue with the additional studies that are already underway or planned.” The research represents an 18-year collaboration with the National Cancer Institute and the US Food and Drug Administration. The safety trial results were simultaneously presented Tuesday at the 22nd International Conference on Brain Tumor Research and Therapy in Norway and published in the New England Journal of Medicine. Virtues of a virus Poliovirus can attach to a receptor on the surface of glioblastoma cancer cells, as well as the surface of cells that make up most solid tumors. “Our strategy did not start out with the intent to use poliovirus in cancer immunotherapy. Rather, Dr. Gromeier made a series of research observations over many years,” said Dr. Annick Desjardins, a co-author of the study and an associate professor of neurology and neurosurgery at Duke. Gromeier discovered that a receptor for poliovirus was “virtually universally expressed on cancerous cells of most tumors,” Desjardins said. Burkitt’s lymphoma is the only solid tumor that lacks this poliovirus receptor, a key to the door allowing the virus to enter and kill cancer cells. To create a cancer immunotherapy based on Gromeier’s discovery, the researchers swapped out the genetic sequence that allows poliovirus to reproduce in normal cells and replaced it with DNA code taken from rhinovirus, the cause of the common cold. This was a “safety measure,” Desjardins explained, so the new engineered virus could not damage neurons and cause polio. However, the genetic modification does not prevent the hybrid virus from replicating inside cancer cells, a process that releases toxins which destroy cancer cells. After conducting animal experiments with the engineered poliovirus, the researchers enrolled and treated human patients diagnosed with glioblastoma beginning in 2012. Treatment starts with an implanted catheter in a patient’s brain, Desjardins said. Next, the engineered poliovirus is infused directly into the tumor through the catheter. Once the total 6½ hours of infusion are completed, the catheter is removed. At higher dosages of the experimental therapy, some of the patients experienced severe inflammation, which resulted in seizures, cognitive difficulties (including confusion and language difficulties) and other side effects such as nausea. The research team restricted itself to lower-than-hoped doses, yet they still witnessed noteworthy effects. Overall average survival time for the 61 patients who received the experimental therapy was 12.5 months, compared with 11.3 months for a control group of matched patients who received standard treatment (chemotherapy). Some of the poliovirus therapy patients have shown – and continue to show – remarkable resilience: One who began treatment at age 20 and another who began at age 60 have remained alive for more than 69 months – nearly six years – and are still alive today, according to the authors of the study. “The two longest surviving patients have actually recurred and been retreated,” Bigner said. “With chemotherapy, once patients fail, they are resistant, and they don’t respond.” Getting a positive response to a therapy after cancer reappears is “extremely unusual,” he said, adding that in these patients, cancer may be “converted” into a chronic disease. “Whenever they recur, we’ll just treat them again,” Bigner said. Overall, 21% of the poliovirus patients should remain alive three years after treatment, compared with just 4% of the control patients, statistical analysis suggests. “We are presently enrolling in a phase two trial combining the genetically modified poliovirus with one dose of chemotherapy,” Desjardins said. “We are also enrolling on a trial for pediatric brain tumor patients.” Because it is easier to infuse a therapy into tumors anywhere other than the brain, the researchers expect better results when they use this treatment on other forms of cancer, she said. ’Truly astounding’ “Patients receiving the poliovirus therapy have had surprising and promising clinical outcomes,” said Dr. Bryan Choi, a fellow in the Cellular Immunotherapy Program at Massachusetts General Hospital Cancer Center and the Department of Neurosurgery at Harvard Medical School. “It will be critical to support the study of this treatment and other immune-based approaches for glioblastoma in larger, randomized clinical trials.” Choi, who was not involved in the new study but who has published research on the topic, said that “the poliovirus, which otherwise causes a horrible disease that we’ve sought to eradicate for over half a century, has now been re-engineered to instead target and attack another deadly disease, in this case glioblastoma, which is the worst form of brain cancer.” “Perhaps the most promising aspect is the ability for this modified virus to not only directly kill brain cancer cells but to release tumor antigens,” Choi said. Antigens are toxins that unleash the body’s immune reponse. “The immune system then recognizes these antigens and can mount a potent secondary assault on the remaining tumor,” he said. Follow CNN Health on Facebook and Twitter See the latest news and share your comments with CNN Health on Facebook and Twitter.<doc-sep>The poliovirus could help some patients battle a lethal form of brain cancer, scientists report. An experimental treatment seems to have prolonged the lives of a small group of patients with a type of brain cancer called glioblastoma, according to research from Duke University, published on Tuesday in The New England Journal of Medicine. "I've been doing this for 50 years and I've never seen results like this," Dr. Darell Bigner, the director emeritus of The Preston Robert Tisch Brain Tumor Center at the Duke Cancer Institute, who is helping develop the treatment, told NPR. Glioblastoma is the most common and aggressive cancerous brain tumor in adults. It's the cancer that killed former Vice President Joe Biden's son Beau. Senator John McCain had been diagnosed with it. The outlook for patients with this cancer is often dismal. To develop the new experimental treatment, scientists used a genetically modified version of the poliovirus because of the virus's ability to inhabit the nervous system cells. One of the virus's genes was removed to prevent it from causing polio, which can cause devastating paralysis, and replaced it with a gene from a harmless common cold. Researchers then infused the engineered virus directly into the brain tumors. The modified virus retains the ability to infect and kill brain tumor cells, and also seems to activate the patient's immune system cells to fight the tumors. This is especially important since glioblastoma patients often have poorly functioning immune systems from cancer treatments like radiation, ABC News Reported. This treatment did come with some risks. Some patients had side effects like seizures, headaches and speech problems. In some instances, there could be inflammation in the brain. According to the results from the clinical trial, among 61 patients with recurrent glioblastoma who received the experimental therapy, 21 percent will survive for three years or longer, compared with only 4 percent of those treated with chemotherapy, the current standard therapy, CNN reported. The scientists were surprised by the results. "You just don't see this percentage of long-term survivors with this disease," Bigner told NPR. "Those that have survived more than two years are in remission, and we expect them to continue to be long-term survivors."<doc-sep>Glioblastoma is a type of brain cancer that has recently been quite visible in the media after Sen. John McCain was treated for it. Glioblastoma claimed the lives of over 15,000 people in 2015. However, researchers at Duke University are working to reduce that number through “oncolytic virus therapy” from an unexpected medical foe: The poliovirus. What is oncolytic virus therapy for cancer? It's a type of treatment from a branch of cancer care called immunotherapy where human viruses, which can fight cancer in different ways, are modified in a lab and used to fight cancer. Through oncolytic virus therapy, the viruses can stimulate the immune system, the same system that fights disease like the flu, to also attack cancer. With this particular form of therapy, the viruses can also infect cancer cells themselves, making them break apart and die. Viral therapy arose many years ago when spontaneous tumor remissions happened after immunizations with live, weakened viruses. There have been studies using viral therapy in lung cancer and melanoma, with an actual viral therapy approved for melanoma by the U.S. Food and Drug Administration (FDA) in 2016. Why use it to treat this brain cancer? Brain cancers are rare but if someone does develop brain cancer, it's likely to be glioblastoma. Unfortunately, it has a poor prognosis, with most patients dying about 14 months after it’s diagnosed. That's not just because of a high tendency for malignancy, but also because of its resistance to current cancer treatments: surgery, radiation, and chemotherapy. The reality of the glioblastoma prognosis has caused some patients to choose to end their lives soon after diagnosis. New treatments are desperately needed, and this particular type of cancer has characteristics that make it an ideal candidate for viral therapy. How does it all work? A live poliovirus is used, weakened by a process in the lab. It’s important to note that live, weakened viruses have been commonplace for years and are critical components of many vaccines worldwide, such as the poliovirus. In the case of oncolytic virus therapy, the poliovirus is genetically modified so that it works like its regular viral self but does not have the ability to cause its “normal” disease. The disease-causing part of the poliovirus, infamous for causing a devastating neurological disease, is taken out and replaced with a part that is harmless. To the immune system, it looks like “the real polio” but does not have the ability to cause the disease, or even mutate to anything that could cause it. This is important, as the modified virus has to maintain the ability to affect the same target, the brain. The virus is also further modified to include components that would stimulate one’s immune system to fight back. Glioblastoma patients often have poorly functioning immune systems, both from the disease and also from treatments like radiation that knock out immunity. By inserting a new segment into the virus, like from the common cold, the immune system gets active without any actual illness. A strong immune system reaction draws cells toward cancer to attack it. Because cancer cells work differently than normal cells, the genetically modified virus interacts differently with cancerous and noncancerous cells. Cancer cells from glioblastoma have different chemical components than noncancerous brain cells. The genetically engineered poliovirus thus has the ability to target cancer cells, infect and take over the cell’s machinery, and encourage a person’s own unique immune system to attack. It does this while leaving non-cancerous cells untouched. Why use the poliovirus? Human viruses are unique, co-evolved with the human immune system, teaching it to recognize and kill infected and abnormal cells. Poliovirus has a large RNA size (RNA is a genetic component), in comparison to other viruses so researchers can play with its parts in genetic manipulation. It also has a limited lifespan in humans, unlike other viruses, such as chickenpox. Thus, it has the potential to be used to treat a number of different kinds of cancers. What have been some of the results? Using polio as a "cancer-killing virus,” researchers at Duke have seen a survival rate at three years of about 21 percent in patients with brain cancer who got the oncolytic virus therapy with the poliovirus. Survival was only 4 percent for those who didn’t receive the therapy treatment. The therapy has been able to be given locally in the brain’s tumor site through a special catheter. This allows more “seeding” of the virus into tumor cells and not spreading throughout the body. Many patients have been able to tolerate the poliovirus therapy well, but some have had side effects such as seizures, headaches, and speech problems. Too much of an inflammatory response can be a bad thing. Higher doses of the poliovirus therapy treatment were associated with more inflammation to the brain. Researchers have been working to address dosing and minimize inflammation without compromising an immune system boost by using bevacizumab, a drug to minimize inflammation during the viral treatment. Poliovirus therapy is still in clinical trials and not ready yet for the general public. Big questions are potential cost, as some current viral therapies are about $60,000 per treatment and the ability of hospitals to transport, store, and discard these drugs are concerns for patients and providers. Where can one learn more? Immunotherapy is still a developing field. Talking to a medical professional and keeping up with results from quality sources, like the Centers for Disease Control and Prevention (CDC) and American Cancer Society, are important ways to find out more. Petrina Craine is an emergency medicine resident physician in Oakland, California, working in the ABC News Medical Unit.<doc-sep>The idea that viruses may be co-opted to do good rather than harm isn’t entirely new; researchers have been attempting to harness the power of viruses and bacteria for more than a century. Vaccines are the shining example of using bad bugs to do good in priming the immune system to fight disease. But disease-causing viruses aren’t always easy to corral, and attempts to use them to activate the immune system against things other than fellow bacteria and viruses — including cancer, for example — have not been so successful. There is only one approved virus-based treatment for cancer, which uses herpes virus against melanoma. In a new report published in the New England Journal of Medicine, however, scientists led by a team at Duke University report they may have trained another virus to target cancer, by using poliovirus to target brain tumors. 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Dr. Darell Bigner, emeritus director of the Preston Robert Tisch Brain Tumor Center at Duke University Cancer Center, and his team engineered a poliovirus that was designed to target a difficult-to-treat brain cancer known as glioblastoma. Among a group of 61 people who had failed to respond to current therapies, which include radiation and chemotherapy, 21% who received the poliovirus treatment were alive after three years, compared to 4% who generally survive that long following standard therapy. The virus-based therapy is the culmination of 20 years of work by Bigner’s colleague Dr. Matthias Gromeier, professor of neurosurgery at Duke, who engineered a poliovirus that could activate the immune system but not cause polio. He accomplished that by swapping out one of the poliovirus’ genes for a similar one found in the rhinovirus that causes the common cold. Poliovirus has evolved to become quite adept at infecting certain human cells, by targeting a molecular door on these cells known as CD155. This door, or receptor, is found on cells in the intestines, and in motor nerves in the spinal cord, which explains why poliovirus infection causes paralysis. (Poliovirus that infects intestinal, cells, however, often doesn’t cause serious health problems or even many noticeable symptoms.) It is also found on many solid tumors as well, including glioblastoma. When Gromeier’s modified poliovirus infected these brain cancer cells, it began to kill some of them. But more importantly, the virus also recruited other immune system cells to launch an attack on the cancer cells. The poliovirus made these additional immune cells “extremely angry,” says Gromeier, which is a good thing for fighting the cancer — but only to a certain extent. An over-activated immune response can cause serious inflammation, and the researchers had to lower the initial dose of the virus therapy, which they injected directly into the tumors in the brain, several times before they found the right balance for an immune attack on the cancer. As aggressive as that initial immune assault can be, however, it can dissipate just as quickly, when the virus starts to die off. Poliovirus is designed to infect cells and reproduce for a few weeks, and once the microbes have done their work in infecting cells, their anti-cancer effect wanes as well. But Bigner and his team are optimistic that they can address that potential shortcoming by taking advantage of other recent advances in immune-based therapies for cancer. They plan on combining their poliovirus treatment with so-called checkpoint inhibitors, which release the immune system to attack tumor cells with more abandon. (Normally the immune system is trained not to attack cancer cells, since they are not foreign intruders like bacteria or viruses, but the body’s own cells that grow out of control.) “It’s a very obvious combination strategy for us that we will pursue,” says Gromeier. So far, Bigner says that eight of the 61 patients are what he considers long-term responders, who have survived longer on the virus-based therapy than they would have if they had received radiation and chemotherapy. Some of their tumors began growing again, but they were treated with another dose of the poliovirus therapy, and were able to stop the cancer from growing. Some were also treated with chemotherapy when the tumors began to grow again, and “many of them responded dramatically; their tumors fell apart,” says Bigner. His group is now conducting another trial to compare people who are treated with the poliovirus therapy alone, or with the poliovirus and a single dose of chemotherapy. The people in the current study had all been treated with standard therapies and saw their cancer return, but Bigner hopes that the results lead to moving the virus-based immune therapy earlier in the disease, when people’s immune systems are stronger and better able to launch an effective attack against cancer. He is also encouraged that the strategy will work against other cancers as well, and plans to start studies with people diagnosed with melanoma and difficult-to-treat triple negative breast cancer. Animal studies hint that the virus could be used against pancreatic, prostate and stomach cancers, too. “I’ve been doing this for 50 years and have never seen responses in a study like this,” says Bigner. “The results, in terms of long-term survival, are better than anything in the literature. And I think we can build on this.”<doc-sep>
Polio was a devastating disease before the development of the polio vaccine. But now, this once-feared virus might help treat another deadly illness — brain cancer. In a new study, some patients who had an aggressive type of brain cancer called glioblastoma and who received a genetically modified poliovirus lived much longer than typical for these patients. The study found that about 21 percent of the brain cancer patients who received the poliovirus therapy were alive three years later. In contrast, among a group of previously treated patients who had the same cancer but received standard therapies (such as chemotherapy), just 4 percent were alive after three years. Still, the new study was small and wasn't designed to determine exactly how effective the poliovirus therapy is, so future studies are needed to look at this question, the researchers said. What's more, it appears that most patients in the study didn't respond to the new therapy at all. [5 Facts About Brain Cancer] But the researchers said that the new results are promising and that they plan to conduct more studies to see if they can increase the percentage of patients who benefit from the treatment. “Glioblastoma remains a lethal and devastating disease," senior study author Dr. Darell Bigner, emeritus director of the Preston Robert Tisch Brain Tumor Center at the Duke Cancer Institute, said in a statement. "There is a tremendous need for fundamentally different approaches" to treat the disease, Bigner said. "With the survival rates in this early phase of the poliovirus therapy, we are encouraged and eager to continue with the additional studies that are already underway or planned." The study was presented on Tuesday (June 26) at the International Conference on Brain Tumor Research and Therapy in Norway and was simultaneously published in The New England Journal of Medicine. New treatment for a deadly cancer People with glioblastoma — the most common type of cancerous brain tumor in adults — typically live less than 20 months after their diagnosis, the researchers said. And patients with a recurrence of this cancer (meaning the cancer appeared to go away and then came back) typically survive less than 12 months. For the new study, the researchers genetically modified the poliovirus so that it can't cause the polio disease or reproduce in brain cells. But the modified virus seeks out cancer cells, and once it infects these cells, it triggers the body's immune system to attack the cancer cells. The study involved 61 patients who had a recurrence of glioblastoma and were treated with the modified poliovirus (which is infused directly into the brain) between 2012 and 2017. These patients were compared with a group of 104 glioblastoma patients with a cancer recurrence who were treated at Duke with standard therapies, before the poliovirus therapy was available. This latter group was called "historical controls." Overall, the median survival for patients who received the poliovirus therapy was 12.5 months, compared with 11.3 months for historical controls. ("Median survival" is the number that's in the middle for survival; that is, an equal number of people survived for a longer amount of time and an equal number of people survived for a shorter amount of time than the median.) While the median survival time for both groups was similar, the researchers saw bigger differences in survival over the long term. After two years, the survival rate among those who received the poliovirus therapy was 21 percent, compared with 14 percent for historical controls, and after three years, the survival rate among the poliovirus treatment group remained 21 percent, while it dropped to 4 percent among historical controls. "It appears that some patients don't respond [to the poliovirus therapy] for one reason or another, but if they respond, they often become long-term survivors," said Dr. Annick Desjardins, an associate professor of neurosurgery at Duke, and co-lead author of the study. The first patient to receive the therapy was Stephanie Hopper, who was diagnosed with glioblastoma when she was just 20 years old and received the poliovirus therapy in 2012, according to CBS News. Now 27, Hopper has finished college, married and become a registered nurse. Initially, the study researchers planned to increase the dose of the poliovirus therapy given to patients, but they found that at higher doses, some patients experienced inflammation that led to serious side effects, such as seizures. So, most patients in the study were given low doses.