Phenotypic And Functional Characterization Of Human Dendritic Cell Subsets Generated In Vitro And Isolated From Tissues
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The immune system defends us against infections and cancer. Dendritic cells (DC) are white blood cells that have a central role to both activate the immune system and to regulate immune responses. In this study, we will determine the functional differences of human DC populations, because a clear understanding of the functional differences between different human DC types is essential for utilizing DC in designing more effective vaccines and immune therapies for clinical applications.
Cytokine Production By Human Dendritic Cells - Is Less More?
Funder
National Health and Medical Research Council
Funding Amount
$378,107.00
Summary
Dendritic cells (DC) are specialist white blood cells responsible for initiating and coordinating immune responses against pathogens and cancer. DC act as sentinels of the immune system and are found throughout the body where they are in constant surveillance for infections or danger signals. Once armed they traffic to the lymph nodes, where they activate T lymphocytes and NK cells, which are then responsible for mounting an attack against the infection or tumour. The complex mechanisms of how d ....Dendritic cells (DC) are specialist white blood cells responsible for initiating and coordinating immune responses against pathogens and cancer. DC act as sentinels of the immune system and are found throughout the body where they are in constant surveillance for infections or danger signals. Once armed they traffic to the lymph nodes, where they activate T lymphocytes and NK cells, which are then responsible for mounting an attack against the infection or tumour. The complex mechanisms of how dendritic cells respond to danger, and how they direct T and NK cells to induce specific immune responses appropriate for a particular infection are poorly understood. Most of our current knowledge of DC has been obtained from mouse studies, and it is believed that secretion of cytokines by dendritic cells play an important role. Human dendritic cells have been difficult to identify, however we have pioneered methods to isolate and characterise them from human tissue. We will therefore investigate the production of cytokines from human DC subsets and the role they play in the induction of immune responses. DC can be instructed in the test tube to recognise a cancer and mount an immune response, and this is a promising new therapy for cancer. Our work will uncover fundamental information about the most potent danger signal, the type of DC and the most important cytokines for inducing immune responses against cancers, and will therefore assist in the development of cancer vaccines.Read moreRead less
Generating Tumour-Specific Dendritic Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such dang ....Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such danger signals are critical for the immune system to respond effectively and for white blood cells of the immune system to find their way to the disease organism and eliminate it. The strongest danger signals are produced by a type of white blood cell known as a dendritic cell (DC). These cells detect infectious agents and produce biochemical alarm molecules that alert the entire immune system to the danger resulting in powerful action against the disease. However, tumours are really just a part of our own body and no danger signal is produced. It is our aim to use genetic modification to make DC see tumours as a threat and produce danger signals. These gene-modified DC either alone, or in combination with other immunotherapies, may lead to destruction of tumours.Read moreRead less
I am an immunologist determining the development and function of the dendritic cell system, including its role in autoimmunity and resistance to infection.
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. The ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project, we will explore how these cells can be used to turn off the harmful cells present in the immune system.Read moreRead less
Role Of Dendritic Cell Subsets In The Generation Of CD4 T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$563,554.00
Summary
This project studies the mechanisms responsible for establishing immunologic memory that is generated by vaccination and determines its efficacy. We aim to identify and study previously unacknowledged factors that critically affect the efficacy of vaccination. The results will be significant for both preventative and therapeutic vaccination (cancer, autoimmunity) and will help us to design new vaccines to improve immune function in infection, autoimmunity and cancer.