Researchers at Massachusetts General Brigham and Dana-Farber Cancer Institute report that a single dose of oncolytic viruses, genetically engineered viruses designed to infect and kill cancer cells, can draw immune cells deep into brain tumors, where they remain active. Their discovery is celldescribes how this approach improved survival rates for patients with glioblastoma, the most aggressive and common form of primary brain cancer, in a recent clinical trial.
“Patients with glioblastoma do not benefit from the immunotherapies that have changed patient care for other types of cancer, such as melanoma, because glioblastoma is a ‘cold’ tumor with poor infiltration of cancer-fighting immune cells,” said co-senior author Kai Wuhelpfennig, MD, PhD, director of the Division of Cancer Immunology and Virology at Dana-Farber Cancer Institute. “The results from our clinical trials and mechanistic studies show that it is now possible to bring these important immune cells into glioblastoma.”
Genetically engineered herpesvirus targets cancer cells
The treatment uses an oncolytic virus developed by E. Antonio Chiocca, MD, executive director of the Center for Neurological Tumors at the Massachusetts General Brigham Cancer Institute. It is based on a modified herpes simplex virus that is designed to replicate only within glioblastoma cells and not affect healthy tissue.
When the virus enters a tumor cell, it destroys it and then produces copies of itself that travel to infect neighboring cancer cells. This process not only directly kills tumor cells, but also activates the immune system. In a phase 1 clinical trial of 41 patients with recurrent glioblastoma, treatment with the virus was associated with longer survival compared to historical outcomes, with the strongest effects seen in patients who already had antibodies to the virus.
Immune response is associated with longer survival
To better understand how this treatment works, researchers analyzed tumor samples taken from trial participants. They found that the treatment resulted in a persistent presence of immune T cells within the tumor. Patients whose cytotoxic T cells were located near dying tumor cells tended to survive longer after treatment.
The treatment also increases the number of T cells present in the brain, suggesting that it strengthens the body’s own immune defenses rather than relying solely on new immune activation.
“We have shown that increased infiltration of T cells that attack tumor cells translates into therapeutic benefit for glioblastoma patients,” said Chiocca, who is also co-senior author of the study. “Our findings could have important implications for cancers where standard treatments have remained unchanged for 20 years.”
In addition to Wucherpfennig and Chiocca, authors include Maxime Meylan, Ye Tian, Lijian Wu, Alexander L. Ling, Daniel Kovarsky, Graham L. Barlow, Linh D. Nguyen, Jason Pyrdol, Sascha Marx, Lucas Westfal, Julius Michel, Sydney Dumont, Andres Santos, Itay Tirosh, and Mario L. Suva.
