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Elucidating The Cellular Processes That Are Critical For P53 Mediated Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$1,016,108.00
Summary
p53 is a tumour suppressor gene that is mutated in ~50% of human cancers. Mutations in p53 cause development of cancer and render malignant cells resistant to chemotherapy. We have identified genes regulated by p53 that appear critical for its tumour suppressive function. In this project, we will use innovative novel genetic tools to discover the cellular and biochemical functions of these genes. The ultimate goal of our studies is to identify novel targets for anti-cancer therapy.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Development Of Cancer Immunotherapy Using Gene-engineered T Cells In A Self-antigen Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$428,602.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells.
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.
Investigating The Anti-tumour Efficacy And On Target Toxicity Of Gene-modified T Cell Therapy In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. Although these cells can induce cancer regression when given back to the patient, these cells can often cause associated pathology. In this study we propose to fully investigate the limits of this type of therapy for mediating anti-tumour responses and potential toxicity in mouse models that closely recapitulate the human setting. These studies will lead to a more effective therapy for patients.
Utilization Of Gene-engineered T Cells For Enhancing Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$761,656.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells, whilst minimizing toxicity to normal tissue.
New Strategies For Enhancing Chimeric Antigen Receptor (CAR) T Cell Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$849,540.00
Summary
The role of the immune system in cancer is now recognised as highly important, highlighted by the success of immunotherapy in patients. Yet many patients fail to respond to this form of treatment due to low frequency of lymphocytes present at the tumor site. A new form of immunotherapy involving transfer of gene-modified lymphocytes is a potential way to overcome this problem. This project will explore new strategies to enhance the utility of this approach against blood and solid cancers.
Regulation Of TNF Expression In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$728,447.00
Summary
By studying a spontaneous mutation in mice, we have found an error in the TNF gene (a major factor in many inflammatory diseases) that causes severe arthritis, heart valve disease and gut inflammation. We have also identified new regulators of TNF expression, which might be useful therapeutic targets to limit inflammation. We intend to study the role of these regulators in controlling the expression of TNF, and the link between chronic inflammation and the development of cancer.
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
Improving Outcomes For Women Diagnosed With Mucinous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,238.00
Summary
Mucinous ovarian cancer (MOC) is different from other ovarian cancers but few studies have characterized the genetic changes specific to this subtype. It is often confused with metastases from other organs and does not respond well to standard ovarian cancer therapies. If MOC is more similar to mucinous cancers from other organs than other ovarian cancers, it may be better treated with chemotherapeutics that show success with other mucinous tumours.