Clinical Data on Novel Oncolytic Virus Treatment for Glioblastoma Published

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Clinical Data on Novel Oncolytic Virus Treatment for Glioblastoma Published

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Clinical Data on Novel Oncolytic Virus Treatment for Glioblastoma Published

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults, with a 5-year survival rate of only around 10%.

It exhibits significant resistance to treatment, and current standard therapies offer only modest relief to GBM patients, with rapid recurrence following surgery and radiochemotherapy. Survival for recurrent GBM (rGBM) patients is typically less than 10 months.

In addition to surgery and radiochemotherapy, traditional immunotherapies have proven ineffective against rGBM, believed to be due to the highly immune-suppressive tumor microenvironment (TME) that hinders the infiltration of anti-tumor lymphocytes. For rGBM and several highly immune-suppressive solid cancers, finding treatment strategies to transform the inhibitory tumor microenvironment into one conducive to immunotherapy and immune activation is essential.

Oncolytic viruses (OVs) present a promising approach to treating solid tumors. When injected into the tumor, oncolytic viruses selectively target cancer cells without affecting normal cells, replicating within cancer cells and causing them to lyse. Furthermore, oncolytic viruses can further stimulate the immune system, making them suitable for combination therapy with other cancer immunotherapies like immune checkpoint inhibitors. Currently, four oncolytic virus therapies have been approved for various cancers, including melanoma, colorectal cancer, and glioblastoma, administered through intratumoral injection.

However, oncolytic virus treatment for recurrent GBM (rGBM) has been lacking sufficient data for immunological characterization associated with treatment outcomes.

On October 18, 2023, researchers from Harvard Medical School Brigham and Women’s Hospital published a study in the prestigious academic journal Nature titled “Clinical trial links oncolytic immunoactivation to survival in glioblastoma.”

This study designed a novel oncolytic virus therapy that could infect cancer cells and stimulate anti-tumor immune responses. This Phase 1 clinical trial demonstrated the safety and preliminary efficacy of this new genetic therapy in high-grade glioma patients, significantly extending the survival of a subgroup of recurrent glioblastoma patients with pre-existing HSV1 antibodies.

Glioblastoma (GBM) is known for its invasive nature, partly due to the immune-suppressive tumor microenvironment surrounding the tumor, which promotes tumor growth by preventing the immune system from entering and attacking the tumor. The research team designed a new oncolytic virus therapy and conducted preclinical experiments, subsequently licensed to Candel Therapeutics, which named this oncolytic virus therapy CAN-3110 and initiated a Phase 1 first-in-human clinical trial.

This oncolytic virus therapy uses oncolytic herpes simplex virus (oHSV), similar to the virus type used in approved oncolytic therapies for metastatic melanoma. However, what sets this therapy apart is the inclusion of the ICP34.5 gene, which is typically excluded from clinical oHSV due to encoding a neurotoxic factor that can cause human diseases.

In this latest research, the research team believed that ICP34.5 may be essential for triggering a potent inflammatory response against tumors. Therefore, the team designed an oHSV1 with the ICP34.5 gene using a nestin promoter, a promoter overexpressed in GBM and other invasive tumors but not in mature human brain or healthy differentiated tissue, ensuring that the ICP34.5 carried by the oncolytic virus would not attack healthy brain cells.

Overall, the clinical trial demonstrated the safety of the CAN-3110 therapy in 41 high-grade glioma patients, including 32 with recurrent GBM (rGBM). The most severe adverse events were seizures in two participants. Notably, the median overall survival of GBM patients with pre-existing HSV1 virus antibodies (66% of the patients) was 14.2 months. In patients with existing antibodies, the research team identified several markers of immune activation-related changes in the tumor microenvironment.

The research team speculated that the presence of HSV1 antibodies led to a rapid immune response against the virus, which brought more immune cells to the tumor and increased the level of inflammation in the tumor microenvironment. After CAN-3110 treatment, the team also observed an increase in T-cell diversity, indicating that the virus induced a broad immune response, possibly by eliminating tumor cells and releasing cancer antigens. These immune changes post-treatment were also linked to improved patient survival.

Looking ahead, the research team plans to conduct prospective studies to further investigate the effectiveness of oncolytic viruses in patients with and without HSV1 antibodies. After establishing the safety of a single virus injection, they are working on testing the safety and effectiveness of up to six injections within four months, similar to multiple rounds of vaccination, which may enhance treatment efficacy.

Professor E. Antonio Chiocca, the leader of the study, stated that there are few immune therapies for GBM that can increase immune infiltration into these tumors. This clinical research with oncolytic viruses triggered a highly active immune response, accompanied by the infiltration of tumor-killing T cells, something that is challenging to achieve in GBM. This study is exciting and offers hope for the next steps.

Link to the paper

Clinical Data on Novel Oncolytic Virus Treatment for Glioblastoma Published

(source:internet, reference only)

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