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.
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Professor Misty Jenkins AO
WEHI
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