Overcoming Obstacles in Brain Cancer Treatment: Innovative Gene Therapy Shows Efficacy Against Glioblastoma

Researchers at Brigham and Women’s Hospital have made significant progress in treating glioblastoma, a notoriously difficult-to-treat form of brain cancer, with a pioneering oncolytic virus named CAN-3110.

In an initial human phase 1 clinical study involving 41 patients suffering from recurrent glioblastoma, the treatment with the oncolytic virus created by Brigham researchers prolonged patient survival, particularly among those who had pre-existing viral antibodies.

The study showcased the therapy’s ability to transform the ‘immune desert’ surrounding the tumor into an inflammatory zone conducive for cancer-fighting. The research validated both the safety and the preliminary effectiveness of this groundbreaking gene therapy for glioblastoma.

Glioblastoma (GBM) is a highly aggressive form of brain cancer known for its resistance to current treatments. Recurrent GBM has a dismal survival rate, typically less than 10 months. Previous immunotherapies have failed to effectively combat GBM, partially because the tumor environment is largely impervious to immune system attacks. The investigators at Brigham and Women’s Hospital, a foundational member of the Mass General Brigham healthcare system, developed a novel oncolytic virus capable of infecting cancer cells and eliciting an anti-cancer immune response. The findings, published in the journal Nature, showed a promising increase in survival among a specific group of recurrent GBM patients who had existing immunity to the virus.

E. Antonio Chiocca, MD, PhD, Chair of the BWH Department of Neurosurgery, stated, “The aggressiveness of GBM is partially due to an environment of immunosuppressive factors around the tumor. Our study reveals that the virus we engineered can modify this immune-inhibitory milieu into an inflammatory one.”

This phase 1 trial was designed to evaluate the safety of CAN-3110, an oncolytic herpes simplex virus (oHSV), which had undergone preclinical testing by BWH researchers and was later licensed to Candel Therapeutics. This virus differs from other oHSVs by including the ICP34.5 gene, usually omitted in clinical oHSVs due to its pathogenic potential in humans. The team hypothesized that this gene might be critical for inducing an effective pro-inflammatory response against the tumor, so they crafted a version of the virus that contains this gene while being programmed to spare healthy brain cells.

The clinical study affirmed the safety of CAN-3110 in 41 patients with high-grade gliomas, 32 of whom had recurrent GBM. Adverse events were limited, with seizures noted in two participants. GBM patients with pre-existing antibodies to the HSV1 virus experienced a median overall survival of 14.2 months. Markers of immune activation were observed, suggesting the pre-existing antibodies may have resulted in a rapid immune response to the virus.

Subsequent to the treatment with CAN-3110, an expansion in the diversity of T-cell types was noticed, indicating that the virus might induce a broad immune response, possibly by eradicating tumor cells and releasing cancer antigens. These immune changes correlated with improved survival rates.

Such research signifies the potential of gene therapy for treating otherwise untreatable conditions. The Gene and Cell Therapy Institute at Mass General Brigham is contributing to the translation of such scientific discoveries into human clinical trials and ultimately into transformative treatments.

Researchers are planning future studies to further probe the efficacy of this oncolytic virus for patients with or without HSV1 antibodies. After establishing the safety of a single viral injection, the team is now moving forward to test the safety and effectiveness of up to six injections over four months. This subsequent trial is financially supported by Break Through Cancer.

E. Antonio Chiocca commented, “Few immunotherapies for GBM have succeeded in enhancing immune cell infiltration into these tumors. The virus we studied elicited a robust immune response, which is a promising development for future treatment strategies.”

Reference: “Clinical trial links oncolytic immunoactivation to survival in glioblastoma” by Ling, AL et al., published in Nature on 18 October 2023. DOI: 10.1038/s41586-023-06623-2

Authorship and disclosures about conflicts of interest and funding sources are listed in the original publication.

Funding for this comprehensive study was acquired from multiple sources including the National Cancer Institute, National Institutes of Health, and various philanthropic organizations and foundations, in addition to in-kind and financial support from Candel Therapeutics, Inc.

Frequently Asked Questions (FAQs) about Glioblastoma Gene Therapy

More about Glioblastoma Gene Therapy

• Clinical Trial Study in Nature Journal
• Brigham and Women’s Hospital Research Department
• Oncolytic Virus Therapy Overview
• National Cancer Institute Glioblastoma Information
• Mass General Brigham Healthcare System
• CAN-3110 Patent Information
• Break Through Cancer Funding Organization
• Candel Therapeutics Corporate Website