Grant: Operating Grant: Targeting High Fatality Cancers - Innovation Grant

A promising class of drugs have emerged on the market in recent years that make use of the patient's own immune system to fight cancer, fulfilling a long-held belief that 'immunotherapy' can help in the treatment of cancer. The drugs called "immune checkpoint inhibitors", or ICIs, are significantly extending the life of patients with advanced stages of melanoma, a disease once thought to be incurable. ICIs are poised to improve survival rates for many other forms of cancer. However, these drugs have some limiting side effects and there is still much room for improvement. We have recently discovered that a family of experimental drugs, called Smac mimetic compounds, or SMCs, which have proven safe in phase I/II cancer trials, can also make use of the immune system to dramatically increase the effectiveness of ICIs in several animal models of cancer. We have obtained a significant amount of preliminary and published data showing that ICI treatment in combination with SMCs can cure mice of glioblastoma (brain cancer) as well as breast cancer and multiple myeloma. In this proposal we seek to understand the broad based nature of this combination cancer immunotherapy and to decipher the way(s) that SMCs improve ICI activity against brain tumours. Our studies will help to justify the initiation of combination immunotherapy trials (using ICIs and Smac mimetic compounds) for brain cancer patients who are in dire need of effective therapies. Moreover, we believe that our approach will be amenable to treating many, if not all, forms of cancer.