Modified herpes virus boosts immune attack against deadly brain cancer
A single injection of a genetically engineered herpes virus can reprogram the immune environment of glioblastoma, one of the deadliest forms of brain cancer, by drawing cancer fighting T cells into tumors that have long resisted immunotherapy, researchers reported this week.
The findings, published Monday in the journal Cell by scientists from the Dana Farber Cancer Institute and Mass General Brigham, provide mechanistic evidence that an oncolytic herpes simplex virus can overcome the highly immunosuppressive nature of glioblastoma and extend patient survival.
In a phase 1 clinical trial involving 41 patients with recurrent glioblastoma, treatment with the oncolytic virus known as CAN 3110 led to sustained infiltration of immune T cells into tumors and improved survival compared with historical benchmarks. The benefit was most pronounced in patients who already had antibodies against the herpes simplex virus.
Among these seropositive patients, who accounted for roughly 66 percent of participants, median overall survival reached 14.2 months. By contrast, patients without preexisting antibodies had a median survival of 7.8 months. Recurrent glioblastoma typically carries a median survival of six to nine months.
Kai Wucherpfennig, senior co author of the study and chair of cancer immunology and virology at Dana Farber, said glioblastoma has not responded to immunotherapies that have transformed care in cancers such as melanoma because it is considered an immunologically “cold” tumor, with low levels of cancer fighting immune cells. He said the clinical and mechanistic data now show it is possible to bring these critical immune cells into glioblastoma tumors.
The oncolytic virus was developed by senior co author E Antonio Chiocca at the Mass General Brigham Cancer Institute. Engineered from the herpes simplex virus, it is designed to replicate selectively within glioblastoma cells while sparing healthy brain tissue. As the virus spreads from cell to cell, it destroys tumor cells and triggers an immune response that recruits cytotoxic T cells to the tumor site.
The Cell study found that closer proximity between cytotoxic T cells and dying tumor cells was associated with longer survival following treatment. Researchers also observed expansion of preexisting T cells within the brain after administration of the virus.
Chiocca said the data demonstrate that increasing infiltration of tumor attacking T cells translates into measurable therapeutic benefit for patients with glioblastoma. He added that the results could have significant implications for a cancer whose standard of care has changed little in the past two decades.
Glioblastoma remains the most common and aggressive primary brain tumor in adults. Even with surgery, radiation and chemotherapy, median survival after standard treatment ranges from 12 to 15 months. Its resistance to immunotherapy has slowed progress for years, leaving patients with limited options. Researchers say the new approach may represent a potential turning point in efforts to harness the immune system against this formidable disease.
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