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Engineered Polio Virus Tested as Brain Cancer Treatment

Brain tumor graphic

(National Science Foundation)

27 June 2018. Results of a clinical trial show a genetically engineered polio virus helps more people with glioblastoma, an aggressive form of brain cancer, survive for longer periods. A description of the treatments and findings were presented this week at the 22nd International Conference on Brain Tumor Research and Therapy in Bjørnefjorden, Norway and appear in yesterday’s issue of New England Journal of Medicine.

A team largely from Duke University in Durham, North Carolina led by cancer researcher Darell Bigner, is seeking more effective therapies for glioblastoma, an aggressive brain cancer that affects astrocyte or glial cells supporting neurons or nerve cells in the brain. Glioblastoma is often difficult to treat, where usually the best hope is to slow progression of the disease with radiation or chemotherapy. American Association of Neurological Surgeons cites data from National Cancer Institute showing glioblastoma accounts for just over half (52%) of all primary brain tumors in the U.S., and 17 percent of all brain cancers, including tumors spread from other parts of the body. Survival from initial tumors is typically 20 months and those with recurring glioblastoma usually survive for less than a year.

In their study, Bigner and colleagues tested a new type of immunotherapy for glioblastoma that starts with a polio virus similar to the Sabin type 1 polio vaccine. The researchers genetically modified the virus to include parts of the human rhinovirus, responsible for the common cold, to reduce its ability to cause disease. But the engineered polio virus still seeks out characteristic receptor proteins found on glioblastoma and other solid tumors, breaks down tumor cell membranes to release antigens that provoke an immune response, and also stimulates an immune response in the microenvironment supporting the tumor’s growth.

The clinical trial is an early-stage study testing the safety and feasibility of the treatments, code-named PVSRIPO, to determine a safe dosage, but the trial also tracks progression-free and overall survival times of participants. The study enrolled 61 patients in grade 4, the most malignant stage of recurring glioblastoma, who received infusions of PVSRIPO directly into the tumor with an implanted catheter. The team found the lower doses of PVSRIPO were generally well tolerated, but the higher doses resulted in hemorrhaging and inflammation in some cases, with nearly 1 in 5 (19%) experiencing severe or life-threatening adverse reactions. About 7 in 10 participants (69%) experienced mild or moderate adverse effects from the treatments.

The trial did not have a control or comparison group, but instead matched participants to an historical control group. The results show PVSRIPO participants overall with a median survival time of 12.5 months, slightly better than the 11.3 months in the historical comparison group. Survival rates remained similar for the two groups until 24 months, when the remaining 21 percent of PVSRIPO recipients continued to survive to 36 months, and 3 participants survived to 60 months. In the comparison group, however, glioblastoma patients’ survival declined to 14 percent at 24 months, with only 4 percent surviving at 36 months.

“With the survival rates in this early phase of the poliovirus therapy,” says Bigner in a university statement, “we are encouraged and eager to continue with the additional studies that are already underway or planned.” Bigner and Duke colleague Matthias Gromeier in 2016 founded the company Istari Oncology Inc. in Chapel Hill that licenses the technology and is developing PVSRIPO as a cancer treatment. Istari took part in this first clinical trial, and is collaborating with National Cancer Institute and others in an intermediate-stage trial testing PVSRIPO with the brain tumor drug lomustine, and an early-stage trial of PVSRIPO in children with brain tumors.

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