Glioblastoma Breakthrough: Virus Triggers Immune Response to Kill Tumours
A single injection of a modified herpes virus has demonstrated the ability to stimulate the immune system to attack glioblastoma, one of the most aggressive forms of brain cancer, according to research published this week.
The findings, stemming from a clinical trial led by researchers at Mass General Brigham and Dana-Farber Cancer Institute, reveal that the genetically engineered virus not only kills cancer cells but also attracts and activates immune cells within the tumor itself. This immune response, researchers found, correlated with improved survival rates in patients with recurrent glioblastoma.
Glioblastoma has historically proven resistant to immunotherapies effective against other cancers, such as melanoma, due to its “cold” tumor environment – characterized by a lack of immune cell infiltration. “Patients with glioblastoma have not benefited from immunotherapies that have transformed patient care in other cancer types…due to the fact that glioblastoma is a ‘cold’ tumor with poor infiltration by cancer-fighting immune cells,” explained Kai Wucherpfennig, MD, PhD, chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute.
The therapy utilizes an oncolytic virus, developed by E. Antonio Chiocca, MD, PhD, Executive Director of the Center for Tumors of the Nervous System at Mass General Brigham Cancer Institute. This modified herpes simplex virus (HSV-1) is engineered to replicate only within glioblastoma cells, sparing healthy tissue. As the virus spreads and destroys cancer cells, it triggers an immune response, drawing in critical immune fighters.
A phase 1 clinical trial involving 41 patients with recurrent glioblastoma showed the oncolytic virus treatment extended survival compared to historical data. Researchers at MD Anderson Cancer Center are also working to identify biomarkers in patients’ blood that can predict who will benefit most from treatment with a similar engineered oncolytic virus, Delta-24-RGD. “Identifying a biomarker of response after treatment allows us to identify patients who are responding to therapy early in their course,” said Chibawanye Ene, M.D., Ph.D., assistant professor of Neurosurgery at MD Anderson.
The virus functions by infecting glioblastoma cells, leading to their destruction and subsequent viral replication, further amplifying the immune response. The research published in Cell details how this approach successfully brought immune cells into the glioblastoma microenvironment, a significant hurdle in treating this type of cancer.
Further research is ongoing to optimize the therapy and identify the patients most likely to respond. Researchers are currently investigating whether combining the oncolytic virus with other immunotherapies could further enhance its effectiveness.