TACI: A Novel Immune Checkpoint In Chronic Lymphocytic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$874,462.00
Summary
Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. CLL cells actively shut down immune defenses in patients. Moreover, current as well as emerging more targeted therapies suppress immunity and over a quarter of patients will die from an infection despite a good response to cancer treatments. Our laboratory has gained new understanding in the mechanism of action of a new treatment for CLL called Ibrutinib. This information allows us to design improved treatment options for CLL.
Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. I will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
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.
Combinatorial Therapeutics In High-risk Infant Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$340,891.00
Summary
Modern therapies for children with leukaemia are curative in more than 90%. In contrast, survival for infants less than one year of age at the time of diagnosis is less than 50%. Better therapies are desperately needed. From laboratory testing we have discovered effective novel cancer drugs, which are not currently used for treatment of babies with leukaemia. We will evaluate novel drug combinations and test them in model systems, such that they can be fast-tracked to the clinic.
MRNA Expression Profiling Of Chronic Lymphocytic Leukaemia (CLL) Cells From In Vivo Hypoxic Microenvironmental Niches; Applications For In Vitro Research And Clinical Management.
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Chronic lymphocytic lymphoma (CLL) is the most frequently diagnosed leukaemia in adults and is still considered incurable. CLL cells proliferate in the lymph nodes and bone marrow; these are areas of the human body that are hypoxic when compared to blood. These hypoxic areas affect CLL cell survival, proliferation and treatment resistance. Changes that occur to CLL cells in these areas can be measured by gene expression profiling and modeled in a lab setting to identify targets for treatment.
Targeting Drug-Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$649,048.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease, particularly for patients that develop drug-resistance such as those at the time of relapse.