In collaboration with medical oncologists A/Prof Helen Wheeler, Dr Connie Diakos, Prof Stephen Clarke, A/Prof Nick Pavlakis and Dr Malmaruha Arasaratnam, and radiation oncologist Prof Tom Eade and others, our immunotherapy and targeted therapy research is aimed at improving the treatment of cancer in combination with standard and novel therapies; external beam radiotherapy, chemotherapy and nanomedicine.
136 clinical trials for cancer in Australia include immunotherapies
7 cancers approved by the TGA for treatment with immunotherapies
3 immunotherapies are available on the PBS
Immunotherapy Research Group Leader: Dr Kelly McKelvey
Dr McKelvey is a Post-doctoral Research Fellow whose research achievements have been recognised by a The Brain Cancer Group and Sydney Vital Inflammation Flagship Fellowship and subsequently the inaugural Matt Callander ‘Beanie for Brain Cancer’ HMRI Research Fellowship funded by the Mark Hughes Foundation. Her expertise is in preclinical models of cancer, principally brain cancer, with a major focus of her research being the immune response to multi-modal therapies, including radiation, chemotherapy, immunotherapy, and nanomedicine to increase treatment efficacy and improve patient survival. Her work is contributing to the growing field of research into the role of the immune system in tumour growth and recurrence, and the synergistic effects of combining immunotherapy with standard therapies to refocus the immune system to combat cancer.
Projects
1. Unravelling the tumour microenvironment to combat brain cancer
Dr Kelly McKelvey, Dr James Wilmott, Dr Connie Diakos, A/Prof Helen Wheeler, A/Prof Viive Howell
Brain cancers (gliomas) are among the most debilitating and lethal of human cancers, with limited treatment options available. Currently, gliomas are treated with multi-modality therapies (surgery, radiotherapy, chemotherapy, targeted-therapy, and experimental immunotherapy), which can interact in both positive and negative ways to control tumour growth. The development and success of robust new therapies for glioma can only occur by considering and understanding the unique microenvironment in which these tumours develop (i.e. the blood brain barrier and CNS immunity), and the potential impact the different therapeutic interventions have, alone or in combination, on both the tumour and surrounding CNS.
This work utilises preclinical models of brain cancer and the only Small Animal Radiation Research Platform (SARRP; Xstrahl, USA) on the east coast of Australia.
Funding: The Brain Cancer Group; Sydney Vital Translational Research Centre; Matt Callander ‘Beanie for Brain Cancer’ HMRI Fellowship funded by the Mark Hughes Foundation.
2. Define the optimal radiation therapy dose regimen with chemotherapy and check point immunotherapy to achieve brain cancer remission, while mitigating treatment-induced adverse events
Dr Kelly McKelvey, Dr Connie Diakos, A/Prof Helen Wheeler, A/Prof Viive Howell
By defining the inflammatory and tumour response to single and combined therapies we can develop future projects to examine the mechanisms of interaction in order to develop novel therapeutic agents to stabilise, induce or inhibit the response to improve patient outcomes. This aim will also identify neurological and treatment-related adverse events that are translatable to the clinic – i.e. signs that should be closely observed in the clinic as an indication to adjust or cease patient treatment.
Funding: The Brain Cancer Group; Matt Callander ‘Beanie for Brain Cancer’ HMRI Fellowship funded by the Mark Hughes Foundation.
3. Optimise surgical resection with radiation therapy to improve survival and minimise neurological impact
Dr Kelly McKelvey, Dr Michael Biggs, Dr Connie Diakos, Prof Helen Wheeler, A/Prof Viive Howell
First line therapy for patients with brain cancer is ‘maximal safe resection’. This debulking of the tumour is curative (where it is complete or gross total resection) or palliative (where the tumour is close to the ventricles or eloquent brain regions, such as those controlling speech, language, motor and sensory functions) and performed to alleviate mass effect associated with patients’ symptoms – e.g. headaches, seizures, paralysis, and memory problems. Needle biopsies are also performed to provide tissue for brain cancer type and grading to inform patient treatment.
The slower-growing low-grade brain cancers, complete resection is optimal. In high-grade cancers, such as GBM, this is controversial, as 30% of complete resections result in new neurological deficits that do not convalesce; further impairing the patients’ quality of life. With advances in surgical methodology and adjuvant treatment, a 70-80% extent of resection is thought to be sufficient to improve patient survival, and reduce risk of recurrence and neurological morbidity. Studies on the extent of resection and survival are largely retrospective due to ethical restraints ensuring patients are treated with the best standard of care.
The purpose of this study is to compare the survival, recurrence, and neurological morbidity of complete and partial resection, and biopsy with radiation and immunotherapy.
Funding: The Brain Cancer Group; Matt Callander ‘Beanie for Brain Cancer’ HMRI Fellowship funded by the Mark Hughes Foundation.
4. Tissue toxicity and immune-related adverse events of a novel combination therapy for cancer
Dr Kelly McKelvey, Prof Tom Eade
Brain, lung and colorectal cancer collectively account for over 35% of cancer-related deaths in NSW. All three cancers include radiation as a treatment, and further benefit may be gained from radiation therapy (RT) if combined with immunotherapy. Currently data is lacking on the toxicity of this therapy in healthy tissues. This study will quantify tissue toxicity and immune-related adverse events to combined RT and anti-PD-1 immunotherapy in Healthy brain, lung and colorectal tissues. These data will determine the applicability of this therapeutic modality for these cancers, enable further treatment optimisation, and risk stratification of patients to ensure maximum treatment benefit.
Funding: Sydney Vital Translational Cancer Centre Seed Funding
5. Inflammation in Cancer
Dr Kelly McKelvey, Dr Connie Diakos, A/Prof Viive Howell
This project will establish and characterise murine and human organoid models of cancer. These model systems will then be used to study how different inflammatory cells influence tumour biology and responses to immunotherapy and other standard and novel therapies.
Funding: The Brain Cancer Group; Sydney Vital Translational Cancer Centre
6. Predicting the benefit of immunotherapy in patients with lung cancer
Dr Sarah Hayes, A/Prof Nick Pavlakis, Dr Malamaruha Arasaratnam, Dr Viive Howell, Dr Kelly McKelvey
Immunotherapy reactivates and harnesses the body’s immune system to fight cancer. It is showing remarkable results for several cancers, including in NSCLC, the most common subtype of lung cancer. However, it is effective in only 20% of NSCLC patients. Furthermore, there is no marker available to predict who will benefit from treatment and who will not. As a result, oncologists are unable to determine which 80% of patients would benefit more from an alternate treatment. Proteomics is the large scale study of proteins, often performed using high-resolution mass spectrometric technology called SWATH-MS. In this project SWATH -MS will analyse the peripheral blood plasma proteome of patients with lung cancer to identify a ‘protein signature’ that can predict for likelihood of benefit to immunotherapy treatment.
Funding: 2019 Ramsay Research and Teaching Fund Project Award
