Grant: Project Grant

 Immunotherapies in cancer are used to help kick-start the body's natural defences to attack tumours. They are showing highly promising results in many cancer patients, while in others the effect is unfortunately limited, temporary or nonexistent. It is becoming increasingly clear that to broaden the impact of immunotherapies they will generally have to be combined with other therapies. In the case of a major class of immunotherapies- checkpoint inhibitors- a primary approach is to combine with therapies that can make tumour more 'hot' from an immune perspective. In recent work we have shown for the first time that when FUS is combined with microbubbles it can improve the tumour killing effects of a major checkpoint inhibitor. This project has the overall goal of investigating the mechanism of how this happens and how best to harness and control this effect. The work will be carried out in tumours that are located in the liver, as these affect a large number of patients and can benefit from locally applied treatments. The project is divided into three parts. In the first part we will use a cutting edge custom microscope to look directly at the effects of our FUS exposures on blood vessels in a specialized tumour model. This will tell us how vessels are affected, how to hone in on the appropriate settings, and what types of signals to 'listen' to from the bubbles when this is happening. Using this information, we will then use a custom MRI guided FUS system to create a control method for exposing realistic tumour models located in mouse livers. This will involve using the bubble signals as feedback to control the exposures. Finally we will investigate the therapeutic effects of using this method coupled with an immunotherapy in a realistic liver tumour model. The end result with be a validated new method to potentiate immunotherapy, which has the potential to impact the treatment of a large patient population.