Targeting The NLRP3 Inflammasome And Interleukin-18 In Hypertensive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$1,241,115.00
Summary
Heart failure is a common complication of hypertension and a major cause of death and disability worldwide. This project will characterise a newly identified inflammatory pathway that we believe to be a major cause of the enlargement and scarring of the heart that accompanies hypertension. We will also trial drugs that block this inflammatory pathway to determine their suitability as future therapies for this devastating disease.
Therapeutic Induction Of Tertiary Lymph Nodes In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$995,010.00
Summary
Immunotherapy has been an important recent advance in cancer treatment by using the body's own immune cells to fight cancer. Although there have been unprecedented dramatic results, not all patients benefit, and most benefits are temporary. The cellular environment in which cancers are embedded is crucial for controlling treatment success. We aim to apply novel 'precision' therapies to this environment to expose the cancer and enable attack by immune cells for improved immunotherapy.
Targeting Nerves In Tumours To Enhance Anti-cancer Immunity
Funder
National Health and Medical Research Council
Funding Amount
$1,090,190.00
Summary
The cancer journey is an incredibly stressful experience for patients. We discovered that stress stops immune cells and helps cancer spread. The goal of this study is to reveal how stress signals alter anti-cancer immunity and impacts cancer treatments. We will use elegant tools from neuroscience and immunology to define if blocking stress helps the immune cells that kill cancer and explore how blocking stress can improve standard anti-cancer drugs, including chemotherapy and immunotherapy.
Harnessing Extracellular Matrix Remodelling By Cancer-Associated Fibroblasts To Increase T Cell Infiltration Of Solid Tumours
Funder
National Health and Medical Research Council
Funding Amount
$923,407.00
Summary
The ability of killer T cells to find and eliminate tumour cells is the basis for adoptive transfer immunotherapies, which thus far only work well with blood-borne cancers. There is limited success with solid tumours, which T cells do not readily infiltrate, notably because of remodelling by fibroblasts. We have discovered that T cells migrate in tunnels dug in the tumour matrix by fibroblasts. Here, we will harness this discovery to improve tumour infiltration and rejection of solid tumours.
Ovarian cancer is difficult to diagnose, patients present at a late stage of disease and it responds poorly to therapy. To improve treatment, it is crucial to gain new insights into ovarian cancer biology. We discovered a new protein, interferon epsilon, which is produced naturally by cells lining the female reproductive tract where it protects against infections and may even prevent development of cancers. We plan to characterise the action of IFNe on HGSOC and how best to use it for therapy.
Molecular Dissection Of Allergen Sensitisation And Immunotherapy: Direct Application To Precision Medicine In Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$1,270,097.00
Summary
Asthma is a major global health burden with huge socioeconomic impact. Most asthmatic patients are allergic. Allergen immunotherapy is the only treatment to alter the natural disease course, but does not work in many treated patients, and robust laboratory biomarkers for patient selection and immune monitoring of treatment success are lacking. Therefore, allergen immunotherapy is not offered to most patients who then rely on medications indefinitely. This research will address these needs.
Developing Improved Therapies For Cytomegalovirus Infections By Overcoming Viral Strain Diversity.
Funder
National Health and Medical Research Council
Funding Amount
$1,126,820.00
Summary
Cytomegalovirus infection is the most common cause of infection-related disease in newborns and is one of the most common complications in transplant patients. Current treatments are not always successful and are associated with significant side-effects. We have therefore developed world first systems that can be used to develop safer, more effective treatments for this life-threatening infection. Our findings are likely to be applicable to other difficult to manage viral infections.
The Ins And Outs Of Endocytosis Inhibition: Providing Diverse Opportunities For Treatment Of Incurable Cancers
Funder
National Health and Medical Research Council
Funding Amount
$912,353.00
Summary
The best new immune system anti-cancer drugs only work in ~30% of patients. We found a way to move the drug targets around in people's tumours temporarily to reverse resistance and have tested this in clinical trials. Here we propose to use immunology and the world's frontier electron microscope techniques to work out exactly what is happens to the tumours, immune cells and anti-cancer drugs when they interact in real clinical situations. The aim is to reach at least 60% patient response rate.
Repurposing Thalidomide Derivatives To Augment Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$1,154,196.00
Summary
Immunotherapies are a revolutionary approach for cancer treatment, but most people with cancer do not respond to therapy. We have identified a new set of molecular switches that shutdown immune function and limit responsiveness to existing immunotherapies. Importantly, we have found a class of approved drugs that can block these immune 'off switches'. This proposal will test if these drugs could be repurposed as a novel treatment to amplify the efficacy of existing immunotherapies.
Therapeutic Targeting Of Interleukin-22 For Severe Paediatric Urinary Tract Infection And Associated Renal Complications
Funder
National Health and Medical Research Council
Funding Amount
$997,139.00
Summary
Urinary tract infections are among the most common bacterial infections and are associated with the development of chronic kidney disease. The bacteria that cause these infections are becoming increasingly resistant to antibiotic therapy. Therefore, new strategies that target the immune system rather than the bacteria are urgently needed. This study will provide evidence for re-purposing novel immunotherapies targeting the protein interleukin-22 that are being developed for other diseases.