New Immunotherapy Clinical Trial Uses Modified Poliovirus Against Glioblastoma
The UCSF Brain Tumor Center is one of four sites in the country testing a modified version of a poliovirus that had encouraging results against glioblastoma (GBM) in a recent phase I clinical trial.
In an earlier study published in the New England Journal of Medicine, researchers from Duke University found that nearly 21 percent of recurrent GBM patients treated with the experimental modified virus (PVSRIPO) were alive after three years, compared with 4 percent of patients with similar tumors who received standard therapies. Moreover, the findings indicated that patients who didn’t do as well in the initial study may do better with the modified dose being used at UCSF and the three other sites, according to neuro-oncologist Nicholas Butowski, MD, who is co-leading the UCSF arm with neurosurgeons Manish Aghi, MD, PhD and Mitchel Berger, MD.
In the trial, physicians will infuse a genetically modified, non-pathogenic version of poliovirus into patients’ tumors. Normally, poliovirus can only infect and enter cells by binding to CD155, a protein on the surface of certain cells. PVSRIPO takes advantage of the observation that CD155 levels are high in certain cancer cells, like GBM. Additional modifications ensure that the modified poliovirus only replicates, and goes on to lyse non-neuronal cells. This directly kills tumor cells and also stimulates the immune system to attack the tumor.
Physicians will use convection-enhanced delivery (CED) to administer PVSRIPO directly to the tumor site through a surgically implanted catheter. Half of the patients will receive the study virus only; the other half will also receive a course of the chemotherapy lomustine, which will begin eight weeks after the one-time polio treatment.
To be eligible for the trial, patients must have a recurrent tumor, located in an area that is amenable to CED. UCSF is the only West Coast site for this trial. “We will enroll 31 in each arm, and we hope that by this time next year, we will have some preliminary indications of how the therapy is working,” says Butowski.