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Brain Infusion of Genetically Modified Poliovirus Is Used to Treat Glioblastoma

In This Article

  • Conventional therapies for glioblastoma have overwhelmingly poor treatment results
  • Massachusetts General Hospital is now part of a nationwide phase II trial using an engineered poliovirus to treat glioblastoma
  • Several departments and research institutions across the hospital are collaborating to create new antitumor viruses

Gliobastoma is the most common primary brain tumor and with a five-year survival rate of less than 6% new treatments are sorely needed. Although the development of immunotherapies have been successful in treating malignant cancers, glioblastomas are resistant to such therapies, due, in part, to poor viral infection. However, recent advances have shown that poliovirus can enter and kill glioblastoma cells.

For the first time at Massachusetts General Hospital, William T. Curry, MD, co-director of Mass General Neuroscience and director of Neurosurgical Oncology, is testing a novel therapy that infuses a genetically engineered poliovirus into the brain of a patient to treat the often-fatal brain tumor.

Dr. Curry is the primary investigator of this study at Mass General, which is part of a phase II trial that extends across several U.S. hospitals.

"I am very excited to bring this promising new experimental therapy to our patients," says Dr. Curry. "Early data gives much reason for hope, as we continue the fight to improve the outlook and the survival outcomes for patients with glioblastoma."

The use of the poliovirus to attack cancerous brain cells was first discovered over 20 years ago in a research laboratory. However, in 1991, Robert Martuza, MD, former chief of Neurosurgery at Mass General, first used genetically altered viruses, specifically the herpes simplex virus (HSV), to successfully treat human glioblastoma cells expressed in mice. By 1998, Dr. Martuza and his collaborator, Samuel Rabkin, MD, conducted the first human HSV treatment for glioblastoma, while the first patient for the phase I polio viral therapy was treated in 2012.

"Since the original work started in the late 1980s, more than a dozen oncolytic viruses are in clinical trial worldwide and three are clinically approved for cancer therapy by the FDA in the U.S. or its equivalent in other countries," says Dr. Martuza. "This novel approach is applicable to multiple cancer types."

Now, as researchers learn more about the immune response against tumor cells, it has been demonstrated that oncolytic virus infection of cancer cells generates powerful antitumor immunity. Spurred by Drs. Martuza and Rabkin, more than one hundred publications have come from Mass General research that focuses on creating a new generation of oncolytic viruses engineered to infect glioblastomas while leaving normal brain tissue intact.

Collaborative research efforts between the Departments of Neurosurgery, PathologyRadiation Oncology and the Mass General Cancer Center, along with investigators from the Brain Tumor Research Center, the Brain Science Initiative and the Harvard Stem Cell Institute, have played a critical role in the development of novel therapies.

As the trial proceeds, Dr. Curry and his team are enthusiastic about the potential outcomes. A durable response with these new therapeutic tools will provide a once in a generation change in how this disease is treated.

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