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.
Building A Bridge Between Animal Models Of Blood Transfusion And Clinical Practice: Development Of Sheep Laboratory Models To Investigate The Effects Of Transfusion
Funder
National Health and Medical Research Council
Funding Amount
$86,117.00
Summary
This research project aims to develop clinically-relevant sheep laboratory models of transfusion that will provide a ‘bridge’ between human laboratory and sheep in vivo models and clinical setting by contributing to a better understanding of the underlying mechanisms of transfusion with stored blood products. Ultimately, addressing key knowledge gaps regarding transfusion of aged and cryopreserved blood products will result in improved outcomes for patients.
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.
At least 6 young Australians are diagnosed each day with type 1 diabetes. This Program aims to change the way type 1 diabetes is managed by proactively treating its underlying mechanisms. We will develop safer and more effective immune therapies, develop islet transplantation, look for better markers of disease, and identify ways to preserve insulin-producing cells. The Program aims to propel type 1 diabetes research forward to reach the goals of prevention and cure.
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.
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.
Genetic Determinants Of Interleukin-10 Response After Infectious Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Interleukin-10 is a key protein in the immune defense against infection, being the principal brake for the immune response. An diminished production of interleukin-10 has been implicated as a major cause of a number of devestating medical conditions including septic shock and acute respiratory distress syndrome. An excessive production of interleukin-10 may also be very harmful, and may be the primary cause of the reduction in immune function in many critically ill patients that leads to hospita ....Interleukin-10 is a key protein in the immune defense against infection, being the principal brake for the immune response. An diminished production of interleukin-10 has been implicated as a major cause of a number of devestating medical conditions including septic shock and acute respiratory distress syndrome. An excessive production of interleukin-10 may also be very harmful, and may be the primary cause of the reduction in immune function in many critically ill patients that leads to hospital acquired infections. These potential key roles of interleukin-10 in seriously ill patients makes it an attractive candidate to target for immune therapies. However, past experience with trials of immune-based therapies such as tumor necrosis factor alpha have taught us that we need to be much better at predicting individual immune responses if we are to 'interfere' with the immune system successfully. In the case of interleukin-10 there is substantial individual variation in the amount produced, with studies suggesting up to 70% of this variation is due to genetic differences. This project will establish the basis for this genetic variation by identiying both the genetic markers of high and low interleukin-10 response and the mechanisms by which these genetic markers change interleukin-10 production. This information will not only enable us to better target patients who may need an 'adjustment' of their immune function, but may also lead to novel therapeutic targets or therapeutic agents.Read moreRead less
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.