Common Cold Virus Increases Survival In Brain Tumor Patients

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Highlights:

• Engineered common cold virus, Delta-24-RGD, increases survival in recurrent glioblastoma patients.
• When Delta-24-RGD was injected into the brain tumors, twenty percent of recurrent glioblastoma patients lived for three years longer.
• The virus is non-toxic with minimal side effects and by replicating within cells, they specifically target and kill cancer cells.

Phase 1 clinical trial results show that a common cold virus engineered to attack brain tumors increased the survival rate in twenty percent of recurrent glioblastoma patients. The engineered virus, Delta-24-RGD, added an extra three years or more to the overall survival time in these patients. The study was conducted by a research team at The University of Texas MD Anderson Cancer Center and published in the Journal of Clinical Oncology.

Glioblastoma is an aggressive type of brain cancer that affects astrocytes, a type of cells in the brain that supports neurons. It is difficult to treat, and a cure is often not possible. Treatments are aimed at slowing the progression of cancer. Recurrent glioblastoma is when cancer strikes again after surgery and other treatments. These patients typically have a median survival of 6 months.

Study overview

The clinical trial involved 25 patients with recurrent glioblastoma. The adenovirus called Delta-24-RGD or DNX-2401 was engineered to attack brain tumors. The virus was injected into the tumors of all patients to target the glioblastoma.

‘Engineered common cold virus, Delta-24-RGD, specifically targets cancer cells and triggers an immune response that kills the tumor.’

"We designed DNX-2401 to specifically infect cancer cells, replicate inside those cells to kill them, and spread from cell to cell in a destructive wave throughout the tumor," said senior author and drug co-inventor Juan Fueyo, "The clinical trial shows what happens, as predicted by our preclinical research, and it also shows that in some patients, viral infection was followed by an immune reaction to the glioblastoma that led to the strong responses."

The viral attack

Five of the twenty-five or twenty percent of recurrent glioblastoma patients lived three years longer than the expected survival time. Three out of the five had durable complete responses, which the research team say is exceptional for a phase 1 clinical trial in glioblastoma.

"Many phase I trials might have one patient who does well, so our result is unusual, but we're always cautious in assessing results with this very difficult disease." said lead author Frederick Lang, M.D., professor of Neurosurgery.

The toxicity associated with the treatment was minimal, and the dose escalation went up to the highest concentration of the virus that could be manufactured, which indicates that there were no dose-limiting side effects as well.

Tumor reduction

Seventy-two percent of the patients had some amount of tumor reduction, and the median survival among the patients was 9.5 months.

In the three patients out of the five who achieved complete responses, brain imaging showed that there were inflammation and immune activities even a month after treatment. This is a good sign especially since glioblastomas are normally not recognized by the immune system. A steady decline in the size of the tumor was also observed.

"In the case of these long-term complete responders, the virus breaks the tumor's shield against immune response by killing cells, creating multiple antigen targets for the immune system," said co-inventor Candelaria Gomez-Manzano, M.D., associate professor of Neuro-Oncology. "These tumors are then completely destroyed."

With no detectable tumor, minimal initial side effects and no ongoing treatment, this method of treatment appears to be a better alternative to other methods that come with stronger side effects.

However, even in the three patients who had a complete response, cancer recurred about three or four years later which ultimately became fatal. The recurred tumor appeared as a gliosarcoma in two cases, a tumor different from the original glioblastoma. All three patients lived for at least 4.8 years after treatment.

References:

1. Glioblastoma - (https:www.mayoclinic.org/diseases-conditions/glioblastoma/cdc-20350148)

Source: Medindia

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