PVSRIPO Virus – A New Hope for Glioblastoma

The tumor in the brain sounds horrible to everyone. According to the World Health Organization, there are more than 100 types of brain tumors. Among the tumors, the most common and death-causing malignant tumor is glioblastoma, of which the 5-year survival rate of patients suffering is only 5.1%.

So how can we deal with glioblastoma? Scientists are working on two kinds of ideas. One is the famous CAR-T therapy. In the 2016 New England Journal of Medicine, a case of successful CAR-T treatment of glioblastoma was reported, but CAR-T which costs hundreds of thousands of dollars is expensive and unaffordable for most people.

The other method is viral therapy for glioblastoma which has a unique advantage: the virus injected into humans can activate T cell-led immune response, which is the key to smashing glioblastoma.

Not all viruses can be used to break the tumor, since the brain is very important, and easy to be damaged by viruses while difficult to recover, so many factors must be considered carefully, including toxicity and side effects.

Then, scientists turned their attention to the poliovirus. Although poliovirus can kill neurons and cause polio, this mechanism can be modified to treat glioblastoma. In order to operate a virus to attack cancer cells, it is necessary to change a component called internal ribosome entry site (IRES), which determines the type of cell in which the virus is infected. The IRES of poliovirus can only target nerve cells, so with the help of genetic engineering technology, scientists put the IRES of human rhinovirus type 2 on the poliovirus, which create the key of this experiment - PVSRIPO recombinant virus.

The PVSRIPO virus not only dissolves cancer cells to release antigens and activate immune responses, but also actively infects immune cells such as dendritic cells and macrophages. Infection does not significantly kill immune cells, but activates them to release interferon, attracting more helpers to attack cancer cells, thus developing a dual immune activation capacity.

Based on the result of this experiment, Duke University's research team launched its first clinical trial in 2012 to validate the safety and efficacy of the PVSRIPO virus, and enrolled were 61 patients whose brain tumors were graded to be Level IV, where chemotherapy, surgery and other methods have completely failed.

According to the result, the performance of the PVSRIPO virus exceeded expectations. Among the patients treated, 21% survived for 3 years, and the 2 patients who received the first treatment even survived for 6 years, while the past 3-year survival rate of this kind of patients was only 4%, which means the survival rate has increased for four times.

In terms of safety, PVSRIPO also performed quite well. 69% of patients had only mild adverse reactions, mainly manifested as nervous system symptoms such as headache, convulsions, and hemiparesis. Even with increased dose, only 19% of patients had serious adverse reactions. It is a pity that one patient died of cerebral edema during treatment and may be associated with a viral infection.

"This is a solid step forward, and great progress in fighting with glioblastoma,” said a senior scientist in Creative Biolabs, a company specialized in engineering and construction of oncolytic virus, “but after all, treatment is not effective for many patients, so PVSRIPO therapy is not the final cure for glioblastoma."

Exploration won't stop there. Duke University, along with scientists around the world will do more to explore the therapeutic effects of oncolytic viruses combined with existing chemotherapy drugs, and look for ways to promote the current treatment to a safer and more effective one.