Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
In Vivo Imaging Of Protective And Malignant B Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$431,412.00
Summary
B cells are responsible for producing antibody that protects us from infection. Disruption of healthy B cell function can lead to a myriad of diseases including immunodeficiency, autoimmunity and blood cancers such as leukaemia. The aim of my work is to use powerful microscopy to visualise how mutated B cells interact with their surrounding environment in real-time. These studies will allow the development of new treatments for cancer and immune conditions that target these interactions.
Immunoregulation Of Subsets Of Memory CD8+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$233,867.00
Summary
Information will be sought on the properties of T cells, a class of white blood cells that play a vital role in combating infectious agents. Using mouse models, subsets of T cells that carry immunological memory will be studied and assessed for their rate of cell division and dependence on soluble messengers known as cytokines and other stimuli. The data will provide useful knowledge on the causes of autoimmune diseases (such as rheumatoid arthritis, type 1 diabetes and lupus) and help in the de ....Information will be sought on the properties of T cells, a class of white blood cells that play a vital role in combating infectious agents. Using mouse models, subsets of T cells that carry immunological memory will be studied and assessed for their rate of cell division and dependence on soluble messengers known as cytokines and other stimuli. The data will provide useful knowledge on the causes of autoimmune diseases (such as rheumatoid arthritis, type 1 diabetes and lupus) and help in the development of successful second generation vaccines.Read moreRead less
Immune Imprinting By Nanoparticles And Vaccines: New Principles And Translation Into The Clinic
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Vaccines require adjuvants to be effective. Despite decades of research there is only one adjuvant approved for broad use in humans. Based on our prior findings I will engage new principles in nanotechnology, and deepen understanding of immune imprinting in various organs of the body including the lung, to develop 2nd generation broadly useful nanoadjuvants able to effectively treat cancer and malaria.
Maintenance Of Regulatory T Cells During Inflammation And Tumor Development By IL-33
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Regulatory T cells (Tregs) are required for preventing inflammation in tissues such as lung, fat and skin. We found recently, that the signalling molecule IL-33 is required for tissue Tregs and up-regulated during inflammation and tumor development. We therefore aim to determine the role of IL-33 in maintenance and function of Tregs and to identify molecular targets of IL-33 that may allow therapeutic targeting of Tregs in patients with inflammatory conditions or cancer.
Characterization Of H. Pylori –specific CD4 T Cell Responses And The Evaluation Of The Basic Requirements For The Development Of An Effective Anti-H. Pylori Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$313,161.00
Summary
H. pylori infect over half of the global population. Although infection results in asymptomatic gastritis in most cases 10 % develop gastric ulcers and cancer. Current vaccination strategies have failed to protect humans from infection. We aim to characterise the main immune cells involved in H. pylori infection, specifically the bacteria-specific CD4 T cells. We will then try to understand the basic requirements for a successful vaccine in order to develop new, improved anti-H. pylori vaccines.
TARGETING THE HUMAN CROSS-PRIMING DENDRITIC CELLS FOR IMMUNOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Specialized white blood cells called dendritic cells (DCs) are essential to inducing the immune system to eradicate cancers and viral infections in mice. We have defined human DC subsets and related their functional capacities to the mouse DC subsets. We will now identify the human DC subsets involved in the induction of cancer and viral immune responses and use this information to develop clinical therapeutic cancer vaccination trials.
Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise ....Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise on some recent key technological advances in our laboratory that are enabling us to investigate the mechanisms and the regulation of perforin function. Our recent advances in the field put us in a pre-eminent international position to conduct these studies. In broader terms, the proposed studies will have an immediate impact on our understanding of the mechanisms of cytotoxic lymphocyte regulated immune response and on immune homoeostasis in general. It will also improve our understanding of defence mechanisms against various pathogens and will provide more insight into the role of immune system in protection of the organism against cancer.Read moreRead less
Lymphoid Organ Development: Synthetic Organogenesis Of Artificial Spleen And Characterisation Of Tissue-specific Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$350,232.00
Summary
Spleen is an organ which filters blood circulating around the body and provides immune protection against blood-borne pathogens. Research into spleen development will attempt to synthesise artificial spleen tissue, leading to possible tissue replacement therapies or enhancement of immunity towards infection or cancer. Cellular development in spleen will also be investigated with a view to identifying novel white blood cell subsets that have potential for becoming new targets for immunotherapy.