Research Projects
Immunotherapy
Discovery Theme: Immunotherapy
High grade gliomas in both adults and children are highly aggressive and almost universally fatal. There is an urgent need for new therapies with no new approaches in decades. An exciting new immunotherapy approach to treating cancer is to engineer synthetic receptors, Chimeric Antigen Receptors (CAR), and re-direct a patient’s own T cells to recognise and eliminate their tumour.
CAR T therapy involves the introduction of a synthetically engineered modular receptor into T cells to redirect them to kill tumours, circumventing any requirement for a natural immune response to the cancer. The impressive success of CAR T cell therapy for blood cancers means that further applications of the technology have been sought with accelerating pace. Immunotherapy is changing how we view current therapeutic options and how we look to treat cancer patients in the future. This project aims to change the poor prognosis of brain cancer and make a valuable contribution to cancer immunotherapy.
This comprehensive research program involves: A pipeline of novel target antigen discovery; 2. Generation and functional testing of CAR T cell therapies to adult and paediatric high-grade glioma; and 3. Investigation of brain tumour microenvironment immune profiling. Targeted design approaches will be a major step towards the successful translation of CAR T cells in brain cancers, either alone or in combination approaches to treatment for this deadly disease.
Champions
Laboratory Head, WEHI
Co-Head Research Strategy, The Brain Cancer Centre
Prof Misty Jenkins is a NHMRC fellow and laboratory head at WEHI. Misty leads the immunotherapy program within The Brain Cancer Centre. She is dedicated to discovering novel immunotherapy targets for high grade gliomas in adults and children. Her research focusses on the development of novel chimeric antigen receptor T cells for brain cancer. Her group also uses cutting edge two-photon microscopy combined with mouse models of brain cancer to investigate the tumour microenvironment and uncover unique biology of brain tumours.
Misty has a PhD in Immunology from The University of Melbourne, followed by postdoctoral positions at The Universities of Oxford, Cambridge and the Peter MacCallum Cancer Centre.
Prof Jenkins was awarded the L’Oreal for Women in Science Fellowship (2013), was Tall Poppy of the year (2015), was awarded the Top100 Women of Influence award (2016) and was inducted onto the Victorian Honour Roll of Women in 2020.
Misty co-chairs a Federal Health Medical Research Future Fund (MRFF) and is a passionate advocate for gender equity and Indigenous Health and education. She was awarded an Officer of the Order of Australia (AO) in 2023 for distinguished service to medical science in Immunology, the support of women in STEM, and to the Indigenous community.
Related research projects:
Related videos:
Professor Misty Jenkins AO
WEHI
Senior Research Officer, WEHI
Ryan Cross is a senior research officer in Jenkins Laboratory within the Immunology Division at Walter and Eliza Hall Institute for Medical Research. Ryan is member of the immunotherapy program of The Brain Cancer Centre, with his research focusing on the development of novel immunotherapies for treatment of brain cancer. Early in life, Ryan was inspired by a documentary about Dr John Hammond and his vision to genetically engineer dinosaurs. Disappointingly, after finding out that it wasn’t a documentary Ryan redirected that childhood dream to become an expert in synthetic biology whilst studying for his PhD at the Peter MacCallum Cancer Centre.
Applying his skills in synthetic biology, Ryan is researching how best to genetically engineer the immune system of a person with brain cancer to enhances their immune system’s anti-cancer efficacy. Similar genetic engineering approaches have been successful in blood cancers, however given the increased complexity of brain cancer there is need for a greater level of complexity in the design of synthetic biology for similar success in brain cancer to be realised. Whilst cutting edge genetic engineering may not deliver the pet dinosaur of Ryan’s childhood dreams, he hopes it may provide a future in which those diagnosed with brain cancer are given the opportunity for many nights dreaming of dinosaurs.
Related research projects:
Dr Ryan Cross
WEHI
Co-Head, Brain Tumour Research
The Kids Research Institute Australia
Raelene was awarded her PhD in 2003 from the Harry Perkins Institute for Medical Research (under the supervision of Peter Klinken), undertook postdoctoral training in the Neurobiology and Brain Tumor Program at St Jude Children’s Research Hospital, USA (under the supervision of Suzanne Baker), and was awarded a Fellowship in 2011 to return to Australia to establish the Brain Tumour Research Program at the The Kids Research Institute Australia which she co-leads with Nick Gottardo. This collaborative group of clinicians, neurosurgeons and laboratory scientists uses a suite of in vivo models to understand the effects of paediatric brain tumour mutations on normal brain development and tumorigenesis. Her team also investigates potential therapeutic targets and uses in vivo model systems to evaluate novel treatments prior to clinical trial.
Raelene is a passionate advocate for science and actively encourages young scientists to get involved in medical research. She has mentored high school students, undergrads, Honours, Masters and PhD students in her lab. Raelene has also chaired the The Kids Research Institute Australia Postdoctoral Council and been on the executive committee for the Australian Academy of Science Early-Mid Career Researchers Forum.
Related research projects:
- Developing and characterising unique paediatric brain cancer models to expedite clinical translation
- Immunotherapy
- Mapping the brain’s wound healing immune microenvironment after cancer surgery
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Associate Professor Raelene Endersby
The Kids Research Institute Australia
Theme Leader and Group Head, The Florey, University of Melbourne
Professor Lucy Palmer is head of the Neural Network Laboratory at the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia. She completed her Master of Science at the University of Minnesota, USA and Ph.D at the Australian National University. She then pursued postdoctoral research at the University of Bern, Switzerland and Charite University, Berlin before returning to Australia to establish her research laboratory. Her research uses advanced functional imaging and electrophysiological techniques to investigate how the brain encodes learning and memory in health and disease. She has published articles in high impact journals such as Science, Nature Neuroscience and Nature Communications.
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Professor Lucy Palmer
The Florey, University of Melbourne
Senior Research Officer
WEHI
I am an expert microscopist and trained neurobiologist. Throughout my career imaging has been central to my research, with high impact publications focusing on confocal and multiphoton microscopy both in vitro and in vivo, methods development, quantitative imaging approaches and lightsheet imaging of large cleared tissue samples.
During my PhD thesis I worked with Professor Thomas Kuner at the Max Planck Institute for Medical Research in Heidelberg, Germany, and subsequently joined Nobel Laureate Professor Bert Sakmann’s group at the same institute for my first postdoc. I later moved to Melbourne and used quantitative imaging methods to study epilepsy in Professor Steven Petrou’s laboratory at the Florey Institute of Neuroscience and Mental Health. I managed the Florey’s Microscopy Facility from 2014 to 2017 and joined the Centre for Dynamic Imaging at WEHI in 2017. My areas of expertise include tissue clearing, whole mount and multiplex staining, lightsheet imaging, in vivo multiphoton imaging and various other imaging techniques.
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Dr Verena Wimmer
WEHI
Director of Neurosurgery, The Royal Melbourne Hospital
Professor Kate Drummond, AM, MD, FRACS is Director of Neurosurgery at The Royal Melbourne Hospital and Head of CNS Tumours at the VCCC Parkville Precinct. Her research and clinical interests are in the biology and management of brain tumours, with special interests in advanced surgical techniques such as awake craniotomy, quality of life and blood and imaging biomarkers.
She has published over 190 peer-reviewed papers and many book chapters and has received more than $35 million in research funding. Her h-index is 43. She is Co-Editor-in-Chief of the Journal of Clinical Neuroscience and on the Editorial Board of the Journal of Neurosurgery. She has served as Chief Examiner in Neurosurgery, Chair of the Women in Surgery Committee and on the Neurosurgery Surgical Education and Training Board for the Royal Australasian College of Surgeons, being awarded the RACS medal for these services. She is the President of the Asian Australasian Society of Neurosurgeons.
She is a strong advocate for and has written and presented widely on diversity in neurosurgery. She is Chair of Pangea Global Health Education, a for-impact organisation specialising in health education in low resource settings. In 2019 she was awarded Member of the Order of Australia (AM) for services to medicine, particularly in neuro-oncology and community health.
Related research projects:
- BRAIN POP
- The BRAIN Program
- The Neuroscience of brain cancer
- Deciphering the Molecular Mosaic of NF2
- A novel liquid biopsy for monitoring and chemoresistance detection in brain cancer
- Immunotherapy
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Professor Kate Drummond AM
The Royal Melbourne Hospital
Oncologist/Neuro-Oncologist WCHN
SAHMRI
Prof. Jordan R. Hansford specialises in the treatment of paediatric brain tumours. He is the lead in paediatric neuro-oncology at the Women’s and Children’s Hospital and lead of the Paediatric Neuro-Oncology at the South Australia Health and Medical Research Institute (SAHMRI). He is cross-appointed at the South Australia ImmunoGenomics Cancer Institute at the University of Adelaide. He leads the medical proton integration team and has collaborative preclinical and clinical projects nationally and internationally, and has published widely in paediatric neuro-oncology with over 75 papers cited >5000 times. He is PI or co-PI on several national and international brain tumour studies including early phase studies. He currently runs the paediatric brain cancer biobank in South Australia.
He has been awarded or co-awarded nearly $20M in funding for pre-clinical or clinical trials.
He is an advisor for the Rare Brain Tumours Consortium based out of the Hospital for Sick Children Toronto and the international DIPG Registry. He is a director of ANZCHOG and is the chair of the Neuro-Oncology group. He has led or contributed to many paediatric brain tumour trials leading to disease specific improvements to clinical care and outcomes in many disease types including the practice changing targeted therapy in LGG presented at ASCO 2022. He was invited to participate in the Australian Minister of Health’s National Roadmap to tackle brain cancer and the development of the Australian Brain Cancer Mission and now sits on their board. Most recently the ANZCHOG team has been focussed on the translation of methylation profiling to the upfront diagnostics of paediatric brain tumours that is now offered nationally as a NATA approved pathology test. This has led to changes in clinical practice across the country.
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Professor Jordan R. Hansford
SAHMRI
Division Head, WEHI
Prof Call completed his PhD in Immunology at Harvard Medical School and the Dana-Farber Cancer Institute (Boston, MA, USA) and completed postdoctoral training in solution NMR of membrane proteins at Harvard Medical School. He then established an independent research program at WEHI in 2010. Prof Call’s lab has a particular focus on how the membrane-embedded portions of receptors (transmembrane domains) contribute to the structure and function of immune-signalling complexes and other important cellular receptors. These are not mere anchors for extracellular and intracellular domains, but in fact they provide a unique platform for molecular interactions and represent the only direct physical link between ligand-binding and signalling domains across the cell barriers.
His team combine biochemical and biophysical methods (both X-ray crystallography and solution NMR) with protein engineering, saturating mutagenesis and cellular and molecular immunology techniques to study the mechanics of receptor activation and the regulation of cell-surface proteins in the immune system. A major focus in recent years has been the development (with computational protein design collaborators) and structural characterisation of synthetic transmembrane domains as tools to control the structures and activities of engineered receptors such as chimeric antigen receptors (CARs) for cellular immunotherapies.
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Professor Matt Call
WEHI
Laboratory Head, WEHI
A/Prof Call’s research has a particular focus on how the transmembrane domains of receptors contribute to the structure and function of immune-signalling complexes. These are not mere anchors for extracellular and intracellular domains, but provide a unique platform for molecular interactions and represent the only direct physical link between ligand-binding and signalling domains across the cell barrier.
To understand how receptors are activated and the interactions the make with other proteins we are using deep-mutational scanning to uncover mechanistic insights, such as which areas of the protein are susceptible to disease-causing mutations and how to these relate to the natural function of the receptor. A major focus in recent years has been the development (with computational protein design collaborators) and structural characterisation (by x-ray crystallography) of synthetic transmembrane domains as tools to control the structures and activities of engineered receptors such as chimeric antigen receptors for CAR T-cell immunotherapies.
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Associate Professor Melissa Call
WEHI