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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.
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.
Cancer immunology has emerged as a fundamental discipline of oncology and overwhelming new data from large patient studies reveals the importance of the immune reaction in patient prognosis. Professor Smyth has established a large body of work indicating that the immune reaction is rate limiting for the development of tumours. His previous fundamental work forms a platform to launch new studies that will greatly increase the sophistication with which we understand the various immune mechanisms t ....Cancer immunology has emerged as a fundamental discipline of oncology and overwhelming new data from large patient studies reveals the importance of the immune reaction in patient prognosis. Professor Smyth has established a large body of work indicating that the immune reaction is rate limiting for the development of tumours. His previous fundamental work forms a platform to launch new studies that will greatly increase the sophistication with which we understand the various immune mechanisms that control tumour initiation, growth and metastases. It is a major goal of Professor Smyth’s Australia Fellowship to understand why some tumours may be controlled by the immune response while others are apparently not. He has established mouse models of cancer where these questions can be directly addressed for the first time.Read moreRead less
Investigating The Dynamic Interactions Between Immune And Cancer Cells Using Two-photon Intravital Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therap ....Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therapeutic approaches.Read moreRead less
Identification And Targeting Of A Potent NK Cell “checkpoint” In Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Cancer must evade detection by the immune system in order to develop. Natural Killer (NK) cells can detect and kill cancer cells. We have discovered a potent "checkpoint" in the NK cell activation pathway that desensitizes NK cells to growth factors and switches off their activation and killer function. When this checkpoint is inhibited, NK cells become hyper-activated and prevent most types of cancer metastasis in mice. Targeting this checkpoint in humans could revolutionise cancer therapy
Exploiting The Cross Talk Between Tuft Cells And Group 2 Innate Lymphoid Cells For Tissue Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,162.00
Summary
The project investigates the cellular cross talk within the gastric mucosa between tuft cells, a rare epithelial cell type, and tissue-resident group 2 innate lymphoid cells (ILC2). The tuft cell/ILC2 axis is driven by the two cytokines interleukin (IL)-25 and IL-13 and is required for tissue homeostasis but turns pro-tumourigenic in the context of chronic inflammation. Our investigation will dissect the underlying mechanisms using a combination of mouse models, immunology and bioinformatics.
Identification Of CIS As A Potent Checkpoint In NK Cell-mediated Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$959,596.00
Summary
Cancer must evade detection by the immune system in order to develop. Natural Killer (NK) cells can detect and kill cancer cells. We have discovered a potent "checkpoint" in the NK cell activation pathway that desensitises NK cells to growth factors and switches off their activation and killer function. When this checkpoint is inhibited, NK cells are super activated and can prevent most types of cancer metastasis in mice. Targeting this checkpoint in humans could revolutionise cancer therapy.