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Can Polio Be Used as a Cure for Glioblastoma?—Public Health Watch

JUL 11, 2018 | BRIAN P. DUNLEAVY
The recent “false alarm” regarding the emergence of polio in the troubled country of Venezuela raised the specter of the infectious disease returning to the international stage.

Now, it seems, the complex virus may play a “positive” role in health care—as a potential treatment for glioblastoma, an aggressive form of cancer that begins in the brain or spinal cord, for which there presently is no cure. According to the World Health Organization (WHO), the prognosis for those with stage IV glioblastoma is very poor.

The national incidence rate for the cancer has been estimated at 3.19 cases per 100,000 population annually. Of course, sadly, US Senator John McCain was diagnosed with the disease last year.

However, a study published on June 26 in The New England Journal of Medicine (NEJM) suggests that experiments with a strain of polio may offer McCain and others new-found hope. Investigators from Duke University Medical Center and Deakin University School of Medicine in Geelong, Australia, used convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO) to treat 61 patients with recurrent supratentorial WHO grade IV malignant glioma at 7 different dosing levels ranging from 107 to 1010 50% tissue-culture infectious doses (TCID50), in both a dose-escalation phase and a dose-expansion phase.

Earlier research has concluded that PVSRIPO infects antigen-presenting CD155 receptor cells in vitro, causing sustained proinflammatory cytokine responses and cell activation. This process enables T-cell stimulation, an inflammatory response to the poliovirus that may counter tumor-induced immunosuppression and instigate antitumor immunity.

Believe it or not, this is not the first time a virus has shown “curative” effects against glioblastoma. As Contagion® reported in September 2017, Zika virus was found to kill glioblastoma stem cells by researchers at Washington University in St. Louis, Missouri.

For the more recent NEJM study, median overall survival among all 61 patients who received PVSRIPO at a dose of -1 (5.0×107 TCID50) was 12.5 months—or longer than the 11.3 months in the historical control group used in the research and nearly twice as long as that found in a study of a novel chemotherapeutic regimen. Notably, the survival rate among the patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls.

“In this clinical trial, we identified a safe dose of PVSRIPO when it was delivered directly into intracranial tumors,” the authors note in their concluding remarks. “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. Two patients were alive more than 69 months after the PVSRIPO infusion. Further investigations are warranted.”

A related commentary published in conjunction with the study and written by Dan L. Longo, MD, of Dana Farber Cancer Institute and Lindsey R. Baden, MD, of Brigham and Women’s Hospital, cautions that “a number of questions and problems remain for these viral approaches to cancer treatment. 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 the tumor such that systemic administration is both possible and effective?... Much more needs to be learned, but the clinical results to date encourage further exploration of this new treatment approach.”

Finally, some good news about “bad news” viruses for a change.
 
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous health care-related publications. He is the former editor of Infectious Disease Special Edition.
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