Can Polio Be Used to Treat Glioblastoma?

Investigators have found that a strain of poliovirus—a crippling and deadly infectious disease—may be a potential treatment option for patients with glioblastoma, an aggressive form of cancer for which there presently is no cure.

Investigators from Duke University Medical Center and Deakin University School of Medicine conducted a dose-finding and toxicity study evaluating the convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO) in patients with recurrent World Health Organization (WHO) grade IV malignant glioma.

Previous research has found that PVSRIPO infects antigen-presenting CD155 receptor cells in vitro, causing sustained proinflammatory cytokine responses and cell activation. The process works to enable T-cell stimulation, a response that could potentially counter immunosuppression induced by tumors and instigate antitumor immunity.

For their study, the investigators assessed 7 different dosing levels in 61 patients with recurrent supratentorial WHO grade IV malignant glioma from May 2012 through May 2017; the doses ranged from 10⁷ to 10¹⁰ 50% tissue-culture infectious doses (TCID₅₀) in a dose-escalation phase, followed by a dose-expansion phase.

Patients who received PVSRIPO at a dose level of -1 (5.0x10⁷ TCID₅₀), had a median overall survival of 12.5 months; this was identified as the phase 2 dose. The authors report that a patient who received dose level 5 (10¹⁰ TCID₅₀) was reported to have had a grade 4 intracranial hemorrhage right after the catheter was removed. The investigators deescalated dose 5 to reach the phase 2 dose in an effort to mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use.

For the dose-expansion phase of the study, investigators found that 19% of patients experienced an adverse event of grade 3 or higher that was deemed to have been associated with the treatment.

The investigators report overall survival among patients who received PVSRIPO to have reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months; this percentage was sustained at 36 months. The survival rate among those treated with the therapy proved to be higher than the rate noted among historical controls.

“In this clinical trial, we identified a safe dose of PVSRIPO when it was delivered directly into intracranial tumors,” the authors conclude. “Of the 35 patients with recurrent WHO grade IV malignant glioma who were treated more than 24 months before March 20, 2018, a total of 8 patients remained alive as of that cutoff date.” They added that 2 patients were alive for over 69 months after the PVSRIPO infusion.

Several questions still remain, however, when it comes to using viral approaches for cancer treatment, Dan L. Longo, MD, of Dana Farber Cancer Institute and Lindsey R. Baden, MD, of Brigham and Women’s Hospital, stress in a related commentary that had been published in conjunction with the study.

“How will local administration interact with systemic immunity…? How will the presence or absence of pretreatment immunity to the virus affect the efficacy? Will it be possible to overcome preexisting antiviral immunity, uncertain targeting of the virus to the desired cells, tumor heterogeneity, and possible in vivo genetic changes in the virus and that tumor such that systemic administration is both possible and effective?” they ask.

Clinical results encourage further exploration of these kinds of treatment approaches, they add, and, as such, further investigations are warranted.