Investigator: Matthias Gromeier
Title: Non-pathogenic poliovirus recombinants for the treatment of malignant gliomas
Grantee: Duke University
In the early 2000s, scientists at Duke University embarked upon a bold path for treating brain cancer: killing it with the virus that causes polio. This strategy, although it may at first sound bizarre, in fact has the solid scientific grounding necessary for success in the clinic.
Understanding this bold strategy requires knowing a little bit about polio as a disease. Polio, a highly contagious disease that can lead to paralysis, is caused by a virus that attacks the human nervous system. The polio virus only has the ability to infect certain nerve cells, but it is particularly good at infecting those nerve cells that control movement. It gets into these cells through a protein that lives on their surfaces, which it uses like a gate. The classic symptoms of polio occur when the virus uses this gate to enter nerve cells and then makes so many copies of itself that the cells burst, dying and therefore losing the ability to carry movement-related instructions to muscles of the body.
Scientists studying the polio virus in the context of glioblastoma made a serendipitous observation: many glioblastoma tumors have on their surfaces the very same protein gate that the polio virus uses to enter nerve cells– meaning that the virus should be able to infect tumor cells. Because most normal brain cells do not have this protein gate, the polio virus may give us a way to clear one of the most critical hurdles for new brain cancer treatments: selective targeting and destruction of cancer but not healthy cells in the brain.
In 2002, ABC2 funded early research by Matthias Gromeier at Duke University to exploit brain tumor susceptibility to the polio virus for glioblastoma treatment. In this research, Dr. Gromeier showed that the polio virus could indeed enter and kill patient-derived glioblastoma cells. He then studied how the virus worked inside of cells and modified it for therapeutic use in humans. Finally, he examined brain fluid from patients with glioblastoma for signs of polio immunity that would compromise the effectiveness the new therapy and used this information to identify patients likely to benefit from polio virus-based treatment in a clinical trial.
Since its inception over a decade ago, Dr. Gromeier’s work repurposing the polio virus to treat brain cancer has experienced unprecedented success in both the laboratory and the clinic. Expanding upon the project funded by ABC2, Dr. Gromeier developed a genetically modified version of the polio virus safe for human use. When administered directly into the brain near brain tumors, the modified virus infects cancer cells, makes them burst, and triggers a powerful immune response that targets and kills tumor cells. A Phase 1 clinical trial focused on the safety of this modified virus has shown that the therapy is generally well tolerated in humans and may have considerable therapeutic efficacy against glioblastoma. Ongoing clinical trials with the modified virus thus offer real hope in the search for a brain cancer cure.