Glioblastoma has long resisted the immunotherapy advances that reshaped treatment for cancers like melanoma, largely because the tumor creates an environment that blocks immune cells from entering. That resistance now has a potential answer.
Researchers from Mass General Brigham and Dana-Farber Cancer Institute have published findings in Cell showing that a single injection of a modified herpes simplex virus can penetrate glioblastoma tumors, kill cancer cells, and draw immune fighters deep into tissue where they have historically been absent. According to the announcement, the therapy was tested in a phase 1 clinical trial involving 41 patients with recurrent glioblastoma and was associated with longer survival compared to historical outcomes.
The virus at the center of the research is an oncolytic virus — engineered to replicate exclusively inside glioblastoma cells while leaving healthy tissue unaffected. Developed by E. Antonio Chiocca, MD, PhD, Executive Director of the Center for Tumors of the Nervous System at Mass General Brigham Cancer Institute, it works by destroying each tumor cell it infects, then producing copies of itself that spread to neighboring cancer cells. That chain reaction does more than eliminate cells directly. It also activates the immune system.
The strongest survival benefit was observed in patients who already carried antibodies against the virus before treatment.
To understand the underlying mechanism, the research team analyzed tumor samples from trial participants. They found that the therapy produced a sustained presence of cytotoxic T cells within the tumors — not a brief spike, but a persistent immune response. Patients whose cytotoxic T cells were located closer to dying tumor cells survived longer after treatment. The therapy also increased the number of existing T cells in the brain, suggesting it amplifies the body’s existing defenses rather than depending entirely on new immune activity.
“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,” said co-senior author Kai Wucherpfennig, MD, PhD, chair of the Department of Cancer Immunology and Virology at Dana-Farber Cancer Institute. “Findings from our clinical trial and our mechanistic study show that it is now feasible to bring these critical immune cells into glioblastoma.”
Glioblastoma is the most aggressive and common form of primary brain cancer. Its standard of care has not changed in two decades, a fact Chiocca cited directly. “Our findings could have important implications for a cancer whose standard of care hasn’t changed for 20 years,” he said as co-senior author of the study.
The findings, published in Cell, are the result of both the clinical trial data and a separate mechanistic analysis of how the immune response was triggered and sustained — giving researchers a clearer picture of why some patients responded more strongly than others.
The research team’s next step, as stated in the findings, is to explore how the increase in T cell infiltration translates into broader therapeutic benefit for glioblastoma patients.
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