Researchers expanding use of poliovirus for cancer treatment

Duke researchers at the forefront of the field of immunotherapy are working toward applying a modified poliovirus to treat prostate and eventually breast cancer.

Investigators at the Duke University Medical Center are using a modified form of polio to teach the body’s immune system to find and destroy cancerous tissue that it normally cannot. Earlier this year, this form of immunotherapy saw measured success in early clinical trials of patients with aggressive glioblastomas—a deadly brain tumor—sending the cancer of certain patients into remission. Dr. Daniel George, medical oncologist and one of the principal investigators, said he hopes the treatment will prove as effective for prostate and breast cancer, two of the most common cancers.

“Duke has been a fantastic environment for this kind of team science with immunotherapy,” George said. “It really makes it possible to take an exciting finding in brain tumors and bring it into a number of other settings like prostate cancer.”

Dr. Matthias Gromeier, associate professor of neurosurgery at Duke, was the first to propose using poliovirus to destroy malignant tumors. Although cancer is skilled at evading the notice of the immune system, the poliovirus helps alert the body’s defenses to the presence of malignancies. Gromeier was able to engineer a harmless version of the virus that could enter tumor cells. By targeting tumor cells in sites where the cancer has metastasized, the modified virus initiates an inflammatory response from the immune system, allowing it to recognize the tumor as dangerous and potentially attack tumors present elsewhere in the body.

“We are causing an immune response that is what we call ‘systemic’ or ‘whole-body’ from a localized treatment,” George said. “It doesn’t stop the process of metastasis, but it might reverse one of the critical steps necessary for tumors to spread.”

George and co-investigator Smita Nair, associate professor of surgery and pathology, said they hope that this new form of immunotherapy will eventually prove effective on most, if not all forms of cancer, but warned that years of research and trials will be necessary. For optimal accuracy, they are testing the virus one cancer at a time, focusing on more advanced metastatic cancers. Traditional forms of treatment—surgery, radiation and chemotherapy—currently cannot “cure” patients at such advanced stages, George explained, but the re-engineered virus could offer a chance of survival to even these cases.

One focus of current research is whether or not the treatment will prove effective when used on tumors in areas outside the central nervous system.

Polio in its natural form is a disease of the CNS—this does not mean, however, that the re-engineered poliovirus is only capable of acting on brain cancer. Nair confirmed that lab tests showed the virus to be effective on various kinds of tumors, and it should theoretically be capable of infiltrating any cell with a CD155 receptor, a protein that most tumor cells have.

In fact, this form of immunotherapy could prove more effective for cancers outside the CNS, George said. For example, the prostrate glands, unlike the brain, can easily be accessed with a needle. This ease of access could give doctors the option of re-treating the patient if necessary.

Although the prostate cancer research is still in a pre-clinical stage, George said he and his colleagues are very close to being able to present their data to the Food and Drug Administration, which would allow them to move into the first of several phases of clinical trials.

“From developing this as a research approach in clinical trials to something that would actually be commercially available is a long process,” George said. “But we think we’re very close—hopefully within a year or so of bringing it into patients with prostate cancer in clinical trials.”

Correction: The article was modified to include Smita Nair's title, which was missing in a previous version. The Chronicle regrets the error.