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Can gene therapy using herpes virus effectively treat glioblastoma?

MRI image with contrast of WHO grade IV glioblastoma – Image credit Christaras A via Wikipedia

CANCER DIGEST – Nov. 10, 2023 – A genetically engineered anti-cancer herpes virus used as part of a gene therapy approach for recurrent glioblastomia, a deadly form of brain cancer, extended survival particularly in patients who had pre-existing antibodies to the virus, a new early clinical trial shows.

The first-in humans trial by a team of researchers at Boston’s Brigham and Women’s Hospital led by Dr. E. Antonio Chiocca, MD, PhD, Chair of the BWH Department of Neurosurgery, examined the safety of an oncolytic virus, called CAN-3110, an engineered version of the herpes simplex virus that has shown promise in the treatment of metastatic melanoma. The results of the trial were published in the Oct. 18, 2023 journal Nature.

Unlike the virus used in the melanoma trials, however, the BWH team further engineered the virus to include a modified version of a gene that triggers an immune response but not disease.

Glioblastoma (GBM) is an aggressive brain cancer that is stubbornly resistant to treatment, with recurrent GBM associated with survival of less than 10 months.

In the trial aimed at demonstrating safety, 41 brain cancer patients including 32 of whom had recurrent, high-grade glioblastoma, were given a single injection of the new treatment. The results showed several changes in the tumor microenvironment linked to immune system activation, suggesting the virus triggered a rapid immune response.

The researchers also observed an increase in the diversity of the T cells, suggesting that the virus induces a broad immune response, perhaps by eliminating tumor cells resulting in the release of cancer antigens, proteins that mark a cell for targeting by antibodies. These immunological changes after treatment were also linked to improved survival.

Among the 41 patients, nearly two-thirds (66%) of whom had previous exposure to the herpes virus, survived a median of 14.2 months.

“Almost no immunotherapies for GBM have been able to increase immune infiltration to these tumors, but the virus studied here provoked a very reactive immune response with infiltration of tumor-killing T-cells,” Chiocca said in a press release. “That’s hard to do with GBM, so our findings are exciting and give us hope for our next steps.”

Those next steps include a larger trial to further investigate the safety and effectiveness of CAN-3110 using multiple injections over four months.

Source: Brigham and Women’s Hospital press release


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