We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Alpha-particles linked to recombinant antibodies targeting tumour cells have potential to effectively treat tumours while minimising normal tissue side effects. We will explore a novel alpha-particle therapy approach to solid tumours, by delivering 225Ac directly into tumour cells, or into cells that support the tumour (microenvironment). This approach will hopefully result in development of a new approach to treatment of cancers that are resistant to conventional therapies.
Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.
Humanisation And Pre-clinical Validation Of A Therapeutic Anti-cancer Antibody
Funder
National Health and Medical Research Council
Funding Amount
$699,136.00
Summary
This grant will develop a novel antibody against a protease expressed on cancer cells. Preclinical studies, and antibody humanisation, will be performed. This project will also provide vital information on optimal therapeutic approaches with the antibody that can be ultimately taken into human trials.
Characterisation of nanobubbles. Surprisingly, nano-sized bubbles have recently been found to exist in aqueous solutions. Classical theory tells us they should rapidly dissolve, yet they are stable for several days, a phenomenon which has only recently been explained. Despite this, nanobubbles are already used in cleaning processes and appear to have significant health benefits. They are being investigated in treatments for asthma and neurodegenerative diseases. In collaboration with a pharmaceu ....Characterisation of nanobubbles. Surprisingly, nano-sized bubbles have recently been found to exist in aqueous solutions. Classical theory tells us they should rapidly dissolve, yet they are stable for several days, a phenomenon which has only recently been explained. Despite this, nanobubbles are already used in cleaning processes and appear to have significant health benefits. They are being investigated in treatments for asthma and neurodegenerative diseases. In collaboration with a pharmaceutical company, the best means to produce and characterise nanobubbles will be investigated, as well as the conditions governing their stability. The project also aims to determine how the nanobubbles interact with surfaces in order to better control their properties and achieve a better understanding of these bubbles.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100006
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
An adaptable and dedicated linear accelerator for medical radiation research. Leading radiation scientists developing innovative methods and devices for treating cancer patients will collaborate in future research using this highly adaptable linear accelerator for medical radiation research. Innovations in tumour targeting, better patient safety, new medical devices and improved cancer outcomes are expected.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100210
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
In-vivo, high-resolution, whole animal imaging . The purchase of state-of-the-art live-animal imaging equipment for use by researchers at The Australian National University and The University of New South Wales. This equipment will aid the study of many aspects of normal biology and disease including cancer, inflammation, autoimmune diseases and blood vessel disorders.