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Redirecting T-cells For Immunotherapy Of Leukaemia And Lymphoma By The Expression Of A CD19-specific Chimeric Antigen Receptor Using The PiggyBac Transposon Gene Modification System
Funder
National Health and Medical Research Council
Funding Amount
$374,876.00
Summary
Most lymphomas respond to therapy but then relapse. Immune cells can attack and kill virus related lymphomas. However, most lymphomas are NOT virus related. We will create immune cells targeting these virus negative lymphomas by inserting artificial receptors into the immune cells. These receptors attach to the lymphoma and activate the immune cells. The immune cells will home to the lymphoma, kill lymphoma cells and persist in the body for many years, preventing lymphoma relapse.
Leukaemia-cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of these is augmented activity of enzymes called tyrosine kinases including members of the Src family. One called Lyn has been implicated in several leukaemias as well as cancer. We have identified a novel mechanism of down-regulating this family of enzymes mediated by small proteins. These may allow us to develop novel therapeutics for cancer-leukaemia treatment.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Toward Effective Targeted Therapies For Acute Myeloid Leukaemia (AML)
Funder
National Health and Medical Research Council
Funding Amount
$551,345.00
Summary
Standard chemotherapy for acute myeloid leukaemia (AML) is highly toxic, and has not changed in over 40 years. We will conduct a world-first clinical trial incorporating ABT-199 (Venetoclax) to target BCL2 into the standard-of-care treatment for AML. A second initiative will explore the potential for small molecule inhibitors to simultaneously target both BCL2 and its related partner MCL1, to create a “chemotherapy-free” regimen for AML. These studies promise to herald a new era in AML therapy.
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
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. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
Determining The Prerequisites For The Achievement Of Treatment-free Remission In Chronic Myeloid Leukaemia To Facilitate The Development Of New Therapeutic Approaches With Curative Intent
Funder
National Health and Medical Research Council
Funding Amount
$1,318,775.00
Summary
Chronic myeloid leukaemia (CML) can usually be treated effectively with long-term tyrosine kinase inhibitor (TKI) therapy. Remarkably, rare patients who achieve excellent responses can stop treatment altogether without relapsing. Detailed studies of these patients in terms of their genetic background, the biology of their leukaemia and their immune response may help us understand how this is possible, leading to new therapeutic approaches to make treatment-free remission more widely achievable.
Regulation Of Haemopoietic And Immune Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$19,924,984.00
Summary
This Program brings together a team of researchers with world-class multidisciplinary skills in biomedical discovery and an established track record of clinical and commercial translation of research discoveries. This Program will result in the creation of new knowledge regarding the control of blood and immune cell production and function and provide new avenues for the treatment of people suffering from cancers of the blood, inflammatory and immune disorders.
AKR1C3 As A Potential Biomarker For Sensitivity Of T-lineage Acute Lymphoblastic Leukaemia To The Pre-prodrug PR-104
Funder
National Health and Medical Research Council
Funding Amount
$327,797.00
Summary
Multiagent chemotherapy is the most effective modality for the treatment of childhood ALL, the most common paediatric malignancy. Despite dramatic improvements in survival over the past 40 years, relapsed ALL remains one of the most common causes of death from disease in children. Therefore, innovative strategies are needed to benefit those children who respond poorly to established therapy. This application will test a novel therapy for a very aggressive subtype of childhood leukaemia.
Improving Outcomes For Cancer Patients By Targeting The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$2,258,892.00
Summary
The most commonly mutated proteins in cancer involve so called epigenetic regulators, a class of proteins that regulate access to our DNA to control gene expression, DNA repair and replication. We and others have recently developed a variety of drugs to help inhibit the aberrant activity of these epigenetic proteins. My research will focus on ways to improve the efficacy of these existing drugs and find new epigenetic therapies to improve the survival of patients with a broad range of cancers.