Immunotherapy and tumour microenvironment
Tumour microenvironment program
Children with solid cancers that are resistant to standard therapy have a poor clinical outcome. Recent trials in these patients using drugs that release the brakes on the immune system, termed ‘immune checkpoint blockade’, have only had responses in a subset of these patients. To address this issue, VPCC researchers will explore at a deep level each patient’s tumour to better understand if the immune system is responding to the cancer cells. If not, what are the key pathways whereby patients’ tumours escape immune control.
Importantly, VPCC research will identify whether these ‘immune escape’ pathways can be stopped by a conventional treatment or can be targeted specifically by a new drug. Our findings will be used for two key strategies in the clinic (1) to help clinicians decide which patients should receive ICB, (2) to identify what treatments could be combined with immune-based therapies to achieve better clinical outcomes. The VPCC studies will be performed in two key patient groups who currently have poor clinical outcomes. The first is patients with a bone cancer called osteosarcoma with a focus on disease that has spread to the lung. The second is patients with a treatment-resistant sub-type of brain cancer called posterior fossa ependymoma.
Chimeric Antigen Receptor (CAR) T cell therapy is revolutionising cancer treatment in multiple cancer types. However, a major bottleneck to the expansion of these successes is the identification of novel targets that are present on tumours, but not on healthy tissue.
Our vision with VPCC research is to establish ourselves as world leaders in paediatric brain cancer, for both the identification of novel targets and the development of novel immunotherapies to those targets.
Immunotherapy has been the largest advancement for cancer treatment since chemotherapy. Given the delicate location of the brain, therapies must be able to distinguish between healthy and diseased cells, and the power of the immune system provides this discrimination. This project aims to generate novel immunotherapies for paediatric brain cancer. Through generously provided access to patient tumours, we use cutting-edge cell surface proteomics and genetic approaches to map the tumour cell surfaceome and identify immunotherapy targets for paediatric brain tumours. Resulting CAR T cells will be validated in vitro as well as in vivo using our well established orthotopic injection intracranial brain tumour mouse models.
- A/Prof Misty Jenkins – WEHI (Walter and Eliza Hall Institute)
- Prof Ron Firestein – Hudson Institute of Medical Research
- Dr Jason Cain – Hudson Institute of Medical Research
- Dr Peter Downie – Monash Children’s Hospital
- Prof David Eisenstat – The Royal Children’s Hospital/Murdoch Children’s Research Institute
- A/Prof Jordan Hansford – The Royal Children’s Hospital/Murdoch Children’s Research Institute
- A/Prof Paul Neeson – Peter MacCallum Cancer Centre
- A/Prof Paul Ekert – Children’s Cancer Institute
- Prof Joseph Trapani – Peter MacCallum Cancer Centre
- Dr Stacie Wang – The Royal Children’s Hospital
- Dr Deborah Meyran – The Royal Children’s Hospital
- A/Prof Melissa Davis – WEHI (Walter and Eliza Hall Institute)
- A/Prof Andrew Webb – WEHI (Walter and Eliza Hall Institute)
The Immunotherapy program was made possible thanks to generous funding from the National Health and Medical Research Council, the Cure Brain Cancer Foundation, the Isabella and Marcus Foundation, the Robert Connor Dawes Foundation,
Carries Beanie’s 4 Brain Cancer and Cancer Australia.