Molecular & Translational Characterisation Of IMiD-Mediated BET-Protein Degradation In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$497,857.00
Summary
Thalidomide-like drugs (called IMiDs) are an essential treatment for multiple myeloma, a common incurable blood cancer. We have discovered that IMiDs destroy proteins that myeloma cells use to ‘read’ cancer-causing genes in their own DNA. We will therefore investigate how important the destruction of these ‘gene readers’ is in myeloma cells, including patient samples. This will set up future studies targeting ‘gene readers’ using IMiDs in combination with other targeted drugs in clinical trials.
Immunotherapy has recently shown promise in bone cancer. We have found that while immune modulators Il-6 and Ifn?? contribute to tumour suppression Il-23 promotes the growth of radiation-induced bone cancer. We have generated mouse models of bone cancer to investigate tumour growth and immune surveillance in immune competent mice with an overall aim of identifying therapeutic targets in this disease.
Prevention Of Asthma In Young Children Via Immunostimulation
Funder
National Health and Medical Research Council
Funding Amount
$679,683.00
Summary
Persistent asthma is a major problem for Australia yet none of the current therapies do more that control the condition. The long-term solution is to prevent asthma from progressing to the persistent form. The major risk factors are: family history, early allergy and recurrent severe lower respiratory infections (sLRI) in the early life. We will conduct a randomized clinical trial to prevent sLRI using a novel bacterial-derived immunostimulant in infants at high risk of developing asthma.
A Phase I Study Of The First In Class Dual IMiD/bromodomain Inhibitor N-methyl-2-pyrrolidone (NMP) In Relapsed And Refractory Multiple Myeloma.
Funder
National Health and Medical Research Council
Funding Amount
$551,061.00
Summary
We have newly discovered that a simple molecule called NMP has the ability to control myeloma cells that have become resistant to other available treatments. NMP works by enhancing immune function and by killing myeloma cells directly by inhibiting survival signals. NMP is different from all other types of available myeloma treatments. We intend to test the safety and power of NMP in the treatment of myeloma by running a clinical trial of NMP in patients with relapsed myeloma.
Combined T Cell Checkpoint Blockade To Eradicate Established Cancer
Funder
National Health and Medical Research Council
Funding Amount
$207,588.00
Summary
We will use combinations of antibodies to rescue exhausted immune effector T cells in cancers or deplete those T cells that suppress tumor immunity. These exciting new approaches have potential curative impact for the treatment of many human cancers. The mouse has been a useful predictive model and in mice, we will aim to study the combinatorial efficacy and mechanism of action of the most promising antibodies and design a new and more specific means to deplete intratumor regulatory T cells.
Mechanisms Of Regulatory T Cell Induction By Soluble Immunomodulatory Molecules
Funder
National Health and Medical Research Council
Funding Amount
$729,414.00
Summary
The purpose of this work is to identify how a select population of cells (T regulatory cells) function to prevent or dampen down the sometimes-harmful effects of the immune system. Understanding how these cells function may have broad implications for general immune regulation.
Immunotherapeutic Strategies In Anti Myeloperoxidase ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$615,998.00
Summary
Kidney disease is the 10th most common cause of death in Australia. Glomerulonephritis (GN) is a major cause of kidney disease. Autoimmunity underpins disease in most patients with the most severe forms. Following the discovery of the peptide that is the target of this autoimmunity promising new biological treatments are possible. This grant will assess the capacity of four emerging therapies to turn off injurious autoimmunity and treat disease.
We discovered, characterised and commercialised Macrophage inhibitory cytokine-1 (MIC-1/GDF15) for human therapy. Its blood level predicts death from cancer, heart attack/stroke and other diseases. This study will add important information for understandg the actions of this important protein