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.