by A groundbreaking gene therapy called CAN-3110 has been found to effectively target glioblastoma, a highly aggressive form of brain cancer, in early trials conducted by researchers from Brigham and Women’s Hospital. Glioblastoma is notoriously resistant to treatment, with a survival rate of less than 10 months for recurrent cases. Immunotherapies, which aim to activate the body’s immune system to fight cancer, have been largely ineffective against glioblastoma due to the tumor’s ability to evade immune responses. This creates an immunosuppressive environment around the tumor, making it difficult for the immune system to penetrate and attack.
However, the researchers from Brigham and Women’s Hospital have designed a novel oncolytic virus, CAN-3110, that can infect cancer cells and stimulate an anti-tumor immune response, effectively converting the immunosuppressive environment into an inflammatory cancer-fighting zone. The results of the first-in-human phase 1 trial, published in Nature, demonstrated the safety and preliminary efficacy of this novel gene therapy approach in high-grade glioma patients.
The oncolytic virus used in the therapy, CAN-3110, is an oncolytic herpes simplex virus (oHSV) that has been genetically modified to include the ICP34.5 gene, which is typically excluded from clinical oHSVs due to its potential to cause human disease. The researchers hypothesized that including this gene may be necessary to trigger a robust immune response required to attack the tumor. They also ensured that the virus was “programmed” not to target healthy brain cells.
During the trial, CAN-3110 treatment showed promising results in 41 patients with high-grade gliomas, including 32 with recurrent glioblastoma. The therapy had a favorable safety profile, with seizures being the most serious adverse event observed in two participants. Notably, the patients with pre-existing antibodies to the HSV1 virus, which was used in the therapy, had a median overall survival of 14.2 months. These patients also exhibited markers of immune activation and increased inflammation in the tumor microenvironment, indicating a rapid immune response to the virus.
The treatment also led to an increase in the diversity of the T cell repertoire, suggesting a broad immune response induced by the virus. This immune activation was associated with improved survival. The findings highlight the potential of gene therapy in treating challenging conditions like glioblastoma.
The researchers plan to conduct further prospective studies to investigate the effectiveness of the therapy in patients with and without pre-existing antibodies. They also intend to test the safety and efficacy of multiple injections of the therapy over a four-month period, which may enhance its effectiveness. The new trial will be funded by Break Through Cancer.
The success of this study showcases the promise of gene therapy in treating difficult-to-treat conditions. The Gene and Cell Therapy Institute at Mass General Brigham is at the forefront of translating scientific discoveries into life-changing treatments for patients. The multidisciplinary approach of the institute allows for rapid advancement of new therapies and pushes the boundaries of this emerging field.
The researchers are hopeful that their findings and future advancements in gene therapy will pave the way for more effective treatments for glioblastoma and other challenging cancers.
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1. Source: Coherent Market Insights, Public sources, Desk research
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