A groundbreaking gene therapy has shown promise in treating glioblastoma (GBM), an aggressive form of brain cancer known for its resistance to treatment. Researchers from Brigham and Women’s Hospital have developed a novel oncolytic virus that effectively infects cancer cells and stimulates an anti tumour immune response. The results of their study, published in Nature, demonstrate the safety and preliminary efficacy of this gene therapy approach.
GBM has a devastating impact, with less than 10 months of survival associated with recurrent cases. Traditional immunotherapies have not been successful in treating GBM due to the tumours ability to create an environment that is impervious to the body’s immune system. The researchers aimed to transform this immunosuppressive environment into one that facilitates an immune response.
The oncolytic virus used in this therapy, called CAN-3110, is an engineered herpes simplex virus (oHSV), similar to the virus used in a therapy approved for metastatic melanoma. Unlike previous oHSVs, this therapy includes the ICP34.5 gene, which is usually excluded due to its potential to cause disease. However, the researchers believed that this gene was necessary to trigger a robust, pro-inflammatory response required to attack the tumour. The modified oHSV1 was designed not to harm healthy brain cells.
In a phase I clinical trial, the safety of CAN-3110 was assessed in 41 patients with high-grade gliomas, including 32 with recurrent GBM. The most serious adverse events observed were seizures in two participants. Notably, patients who had pre-existing antibodies to HSV1 virus, which accounted for 66% of the patients, had a median overall survival of 14.2 months. These patients also showed markers of immune activation within the tumour microenvironment, indicating a rapid immune response triggered by the virus.
Furthermore, the treatment with CAN-3110 led to an increase in the diversity of T cells, suggesting a broad immune response induced by the virus. This response may be attributed to the elimination of tumour cells, resulting in the release of cancer antigens. The study also revealed that these immunological changes were associated with improved survival.
The Gene and Cell Therapy Institute at Mass General Brigham is at the forefront of translating scientific discoveries into clinical trials and life-changing treatments. Their multidisciplinary approach allows for rapid advancements and pushing the boundaries of gene therapy.
Moving forward, the researchers plan to conduct prospective studies to evaluate the effectiveness of the oncolytic virus in patients with and without HSV1 antibodies. They also intend to test the safety and efficacy of up to six injections over four months, which could potentially enhance the therapy’s effectiveness. The next trial, consisting of six injections, is funded by Break Through Cancer.
Dr. E. Antonio Chiocca, Chair of the BWH Department of Neurosurgery and corresponding author of the study, expressed excitement about the findings, stating that the virus provoked a strong immune response with the infiltration of tumour-killing T-cells. The results offer hope for future advancements in treating GBM, a disease that has been challenging to combat with traditional immunotherapies.
