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.
Production Of Chimeric Monoclonal Antibodies To Pim1, A Novel Therapeutic Target For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$188,850.00
Summary
Almost one in six men will develop prostate cancer during his lifetime. Every year, around 10,000 Australian men are diagnosed and more than 2,500 die of the disease, making prostate cancer the second largest cause of male cancer deaths after lung cancer. The research progress made on prostate cancer over the past 10 years has been encouraging. However the five-year survival rate remains low. There is a vital need to develop new methods to treat this disease. An exciting principle has emerged re ....Almost one in six men will develop prostate cancer during his lifetime. Every year, around 10,000 Australian men are diagnosed and more than 2,500 die of the disease, making prostate cancer the second largest cause of male cancer deaths after lung cancer. The research progress made on prostate cancer over the past 10 years has been encouraging. However the five-year survival rate remains low. There is a vital need to develop new methods to treat this disease. An exciting principle has emerged recently with the use of monoclonal antibodies (Mabs) such as Herceptin (a humanised anti-HER2 Mab), which is now being widely used to treat breast cancer. We produced 2 Mabs to Pim1, which significantly inhibited prostate cancer cell growth in mouse prostate cancer model. Pim1 is a novel oncoprotein, a biomarker for the treatment of prostate cancer as it overexpresses in more than 90% of prostate cancer, but not or less expressed in normal prostate, demonstrated by genearrays and immunohistochemical staining. Pim1 plays an important role in cell survival, proliferation and metastasis. Pim1 is a novel target, and the anti-Pim1 Mabs may be of value for the cancer therapy in humans. However, the murine Mab can not be repeatedly used in human because human would produce anti-mouse antibody response, and the murine Mab would be rapidly removed from circulation, which will greatly limit the therapeutic potential of the Mabs. Fortunately, the problem can be overcome by the use of hybrid chimeric antibodies. In this study, we are going to use chimeric technology to humanise the anti-Pim1 Mab and test them in vitro and in mouse model for the preclinical studies. We have had patent to protect our finding, and we are confident to produce mouse-human chimeric Mab for the future clinical trial as we have proper knowledge, techniques. We are also optimic for the future clinical trial as we have the experiences on commercialisation.Read moreRead less
Targeting The Complement Cascade: A Novel Therapeutic Strategy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$546,496.00
Summary
The incidence of melanoma is increasing world-wide, and Queensland has the highest rate of melanoma in the world. Despite advances in treatment, the 3-year survival rate for metastatic melanoma remains extremely low. This project builds on our recent research demonstrating a role for a key component of the innate immune system (complement C3a) in melanoma growth. Specifically we seek to investigate the potential of C3a as a therapeutic target for metastatic melanoma.
I am a practising hospital physician and a trained scientist and am widely acknowledged at the world leader in my field of study, asbestos cancers. Our latest research discoveries have put us on the threshold of bold new approaches to curing the scourge of these cancers and finding better blood tests but this work now requires extra attention from me to bring it to fruition. A Practitioner Fellowship is an ideal way for me to continue to lead this exciting research.