This project will be the first study of its kind to investigate how effective this new therapy – called STING – will be in eradicating GBM tumours. This project is game-changing from two perspectives (1) this project will explore a new therapeutic approach never tested before in brain cancer and (2) by directly injecting into the tumour, the drug will directly infiltrate the tumour, thus avoiding the issues of passing through the blood brain barrier. This means a much lower dose may be administered while also avoiding unwanted side effects.

This project aims to find a solution for GBM, which currently has no effective therapies. If proven effective, this therapy will open up opportunities for GBM patients to be successfully treated with immunotherapy, which to date has shown little success. Also, once this project determines the therapy is safe and effective in preclinical models, it will advance into a Phase I clinical trial where the drug will be available for GBM patients.

Preclinical validation of a STING agonist to treat Glioblastoma

The prognosis of glioblastoma patients is poor with a median overall survival (OS) of around 21 months. Whereas radiation, chemotherapy and tumour-treating fields are established treatments at initial diagnosis; at recurrence, there are no effective therapies. Immunotherapy for cancer has had unparalleled progress in achieving long-term remissions, even in cases of advanced metastatic disease. Immunotherapy has been adopted as the standard of care for several tumours. In contrast, immunotherapy has not shown efficacy in treating glioblastoma, partly due to immunosuppression. These mechanisms include tumour infiltration by immunosuppressive cells, malfunction or lack of immune-promoting or cancer-killing cells, and frequent use of immunosuppressive drugs such as corticosteroids, among other factors. Recent studies revealed that an immune-promoting protein named stimulator of interferon genes, or STING, can trigger the anti-tumoral immune response in gliomas and melanoma. The project will explore whether STING activation is an effective immunotherapy for gliomas and whether this treatment can be further enhanced by combining it with other immune-promoting strategies/drugs such as PD-1 blockade or signal transducer and activator of transcription 3 (STAT3) inhibition. Here, we propose to investigate this and wish to ultimately determine whether STING agonist drugs are safe and well-tolerated when delivered into the tumours of patients with recurrent glioblastoma, a disease stage that has no effective therapies.