An innovative platform to enhance the efficacy of oncolytic virotherapy for cancer treatment through E-cadherin
Glioblastoma (GBM) is the most common malignant brain tumor accounting for 47.7% of all brain cancers. Unfortunately, treatments are limited, and survival is poor, with approximately 40% living the first-year post-diagnosis and 17% in the second year.
Oncolytic viruses (OVs) are a promising cancer therapy for GBM that infects and lyses cancerous cells in the tumor environment, aiming to stabilize and decrease tumor progression. Moreover, OVs can stimulate the immune system against the tumor cells, influencing the development of the body’s natural antitumor response. Although there are over 40 clinical trials for OVs, only one has been approved by the FDA for the treatment of melanoma. The lack of successful OV-based drugs is primarily due to immune-mediated clearance of the virus and lacking tumor penetration. Hence, new methods to improve OV treatments are needed for many cancers like GBM.
This technology describes the development of a modified herpes oncolytic simplex virus (oHSV) that avoids early clearance and infects tumor cells to promote their destruction via E-cadherin pathway. E-cadherin is a molecule involved in cell migration, and cancer cells lacking E-cadherin are more likely to metastasize. The inventors generated a research-grade prototype of the drug and tested it within xenograph and immunocompetent animal models of GBM. After treatment with the drug, mice exhibited significantly prolonged survival compared to those treated with a placebo.
This technology can be used for GBM and other cancers for which limited treatment options exist.
The technology could reduce and/or eliminate GBM and metastasized cancer cells in other areas of the body or combined with the standard of care. In addition, initial data show that after treatment with the drug, it improves survival in animal models of GBM.