A single injection of an oncolytic virus—a genetically modified virus designed to selectively destroy cancer cells—shows promise in boosting the immune response against glioblastoma, the most common and aggressive form of brain cancer. Findings published in , in the journal Cell detail how this treatment can help immune cells penetrate and persist within brain tumors, potentially prolonging survival in patients with this challenging disease.
Glioblastoma has historically been resistant to immunotherapies that have revolutionized treatment for other cancers, such as melanoma. This resistance stems from the tumor’s “cold” nature—meaning it lacks significant infiltration by the immune cells needed to fight cancer. “Patients with glioblastoma have not benefited from immunotherapies that have transformed patient care in other cancer types such as melanoma because glioblastoma is a ‘cold’ tumor with poor infiltration by cancer-fighting immune cells,” explained Dr. Kai Wucherpfennig, MD, PhD, chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute.
How the Oncolytic Virus Works
The treatment utilizes a modified herpes simplex virus, engineered by researchers at Mass General Brigham, to specifically target and replicate within glioblastoma cells, leaving healthy cells unharmed. The virus effectively kills cancer cells and, crucially, triggers an immune response. This dual action is what sets it apart from other potential therapies.
The research team conducted a phase 1 clinical trial involving patients with recurrent glioblastoma. The trial, identified as NCT03152318 on ClinicalTrials.gov, demonstrated extended survival compared to historical data, particularly among patients who already had antibodies to the virus. This suggests that pre-existing immunity may play a role in the treatment’s effectiveness.
Immune Cell Infiltration and Tumor Response
Further analysis of the trial participants revealed a significant increase in the infiltration of T cells—critical immune cells that directly attack cancer—into the tumor microenvironment. The study showed that the oncolytic virus treatment led to the expansion of pre-existing T-cell clones and sustained T cell-mediated immunity against the glioblastoma cells. This is a key finding, as successful immunotherapy relies on the ability of the immune system to recognize and destroy cancer cells.
Researchers also observed a correlation between the proximity of dying tumor cells (indicated by cleaved caspase-3) and T cells releasing granzyme B (a substance that kills cells) and prolonged progression-free survival. Essentially, the closer the T cells were to actively killing cancer cells, the longer patients’ tumors remained stable. Importantly, the study found that when T cells that had previously infiltrated the tumor expanded in response to treatment, overall survival was also extended. Even as viral remnants remained in areas of tumor necrosis, T cells were able to infiltrate and target live tumor regions.
Implications for Glioblastoma Treatment
“We show that increased infiltration of T cells that are attacking tumor cells translates into a therapeutic benefit for patients with glioblastoma,” said Dr. E. Antonio Chiocca, MD, PhD, Executive Director of the Center for Tumors of the Nervous System at Mass General Brigham Cancer Institute. “Our findings could have important implications for a cancer whose standard of care hasn’t changed for 20 years.”
Glioblastoma remains a devastating diagnosis, with limited treatment options and a poor prognosis. The current standard of care typically involves surgery, radiation and chemotherapy, but these treatments often provide only modest benefits. The potential to harness the power of the immune system to fight this aggressive cancer represents a significant step forward.
The findings suggest that this oncolytic virus therapy could potentially be used in combination with other immunotherapies to further enhance the immune response and improve outcomes for patients with glioblastoma. However, further research is needed to confirm these findings in larger clinical trials and to determine the optimal way to integrate this treatment into the existing standard of care. The researchers emphasize that this is a promising development, but it is still early in the research process.
The study highlights the evolving understanding of the interplay between viruses, the immune system, and cancer. By strategically utilizing a modified virus, researchers are demonstrating the potential to overcome the immune suppression characteristic of glioblastoma and unlock the power of the body’s own defenses to fight this deadly disease.
