Researchers Treat Brain Cancer With Engineered Poliovirus

by Kim Boateng Posted on June 27th, 2018

A genetically modified poliovirus may help some patients fight a deadly form of brain cancer. The experimental treatment seems to have extended survival in a small group of patients with glioblastoma who faced a grim prognosis because standard treatments had failed, Duke University researchers say in a report they presented to the 22nd International Conference on Brain Tumor Research in Norway, on Tuesday.

In the study, only 21 percent of patients experienced a prolonged survival. The researchers and other brain-cancer doctors therefore caution that the research is at a very early stage.

Much more follow-up research is needed to better assess and hopefully improve the treatment’s effectiveness, the researchers say.

“I’ve been doing this for 50 years and I’ve never seen results like this,” says Dr. Darell Bigner, the director emeritus of the The Preston Robert Tisch Brain Tumor Center at the Duke Cancer Institute, who is helping develop the treatment.

“We have to be careful,” says Annick Desjardins, a Duke neuro-oncologist who helped conduct the study. “But we have long-term survivors. We are seeing something we don’t normally see with patients with glioblastoma.”

Dr. David Reardon, clinical director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute in Boston, says the Duke group’s results may represent “a good, solid, important step forward” for patients with no alternatives.

“Unfortunately, for most patients this is not going to be the answer yet,” says Reardon, who used to work at Duke but wasn’t involved in the new research. “My fear is that every patient and family dealing with the devastating disease of glioblastoma is going to think the poliovirus is the cure. Unfortunately, the patients who are benefiting do reflect a relatively small percentage of the population.”

The study which was also published in The New England Journal of Medicine and involved patients with grade IV malignant glioma, also known as glioblastoma. That’s the same type of brain cancer that killed former SenatorTed Kennedy and Beau Biden, the son of former Vice President Joe Biden. More recently, Sen. John McCain, Republican-Arizona, is also suffering from the aggressive cancer and did not receive a positive prognosis.

It was the first human test of this and it didn’t help most patients or improve median survival. But many who did respond seemed to have long-lasting benefit. About 21 percent were alive at three years versus 4 percent in a comparison group of previous brain tumor patients. Similar survival trends have been seen with some other therapies that enlist the immune system against different types of cancer. None are sold yet for brain tumors.

Polio ravaged generations until a vaccine came out in the 1950s. The virus invades the nervous system and can cause paralysis. Doctors at Duke wanted to take advantage of the strong immune system response it spurs to try to fight cancer. With the help of the National Cancer Institute, they genetically modified poliovirus so it would not harm nerves but still infect tumor cells.

The treatment is dripped directly into the brain through a thin tube. Inside the tumor, the immune system recognizes the virus as foreign and mounts an attack.

The National Cancer Institute manufactured the modified virus. Federal grants and several charities funded the work. Some study leaders have formed a company that licenses patents on the treatment from Duke.

Duke has started a second study in adults, combining the poliovirus with chemotherapy, to try to improve response rates. A study in children with brain tumors is also underway, and studies for breast cancer and the skin cancer melanoma also are planned.

Here’s an overview from the National Cancer Institute, NCI, of how researchers are using oncolytic viruses, including an engineered poliovirus, to infect and kill tumor cells

Oncolytic Virus Therapy: Using Tumor-Targeting Viruses to Treat Cancer

For more than a century, doctors have been interested in using viruses to treat cancer, and in recent years a small but growing number of patients have begun to benefit from this approach.

Some viruses tend to infect and kill tumor cells. Known as oncolytic viruses, this group includes viruses found in nature as well as viruses modified in the laboratory to reproduce efficiently in cancer cells without harming healthy cells.

To date, only one oncolytic virus—a genetically modified form of a herpesvirus for treating melanoma—has been approved by the Food and Drug Administration (FDA), though a number of viruses are being evaluated as potential treatments for cancer in clinical trials.

Oncolytic viruses have long been viewed as tools for directly killing cancer cells. But a growing body of research suggests that some oncolytic viruses may work—at least in part—by triggering an immune response in the body against the cancer.

When a virus infects a tumor cell, the virus makes copies of itself until the cell bursts. The dying cancer cell releases materials, such as tumor antigens, that allow the cancer to be recognized, or “seen,” by the immune system.

“Oncolytic viruses are alerting the immune system that something’s wrong,” said Jason Chesney, M.D., Ph.D., director of the University of Louisville’s James Graham Brown Cancer Center. This can lead to an immune response against nearby tumor cells (a local response) or tumor cells in other parts of the body (a systemic response).

For this reason, some researchers consider oncolytic viruses to be a form of immunotherapy—a treatment that harnesses the immune system against cancer. But many in the field would agree that more studies are needed to learn how different oncolytic viruses work against cancer.


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