Mechanisms Of Dendritic Cell-induced T-cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
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 suceptibility to autoimmune disease, the mechanisms fail and the body's immune sytem attacks normal tissues or organs. We have developed a new approach to using the cells which train the immune system to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. Thes ....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 suceptibility to autoimmune disease, the mechanisms fail and the body's immune sytem attacks normal tissues or organs. We have developed a new approach to 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 cells of the immune system and if cells of the immune system in turn control the dendritic cell's ability to do this.Read moreRead less
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.
Defining The Role Of Kidney CD103+ Dendritic Cells In Kidney Disease For Potential Therapies
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Chronic Kidney Disease (CKD) is a major cause morbidity. Dendritic cells (DCs) play a central role in the development and progression of CKD. This research is based on our recent novel finding in which CD103+ DCs have been defined, for the first time, as a major subset of kidney DCs, and shown to be pathogenic in many kidney diseases. This research will further investigate the role of CD103+ DCs in various types of CKD and aim to develop therapeutic strategies to target CD103+ DCs to treat CKD.
Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
A Dendritic Cell Subset Targeting Approach For Generating Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$678,492.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
Targeting Human Dendritic Cells In A Multiple Myeloma Humanized NOD/SCID Model
Funder
National Health and Medical Research Council
Funding Amount
$425,696.00
Summary
Adoptively transferred dendritic cells (DC) loaded with tumor associated antigen (TAA) have been shown to induce anti-tumor immunity in animal models; however, their therapeutic efficacy in cancer patients has not been established. Protective immunity has failed in the tumor-bearing host and the ability of human DC to induce anti-tumor responses in the abnormal environment of the cancer patient requires further investigation. Due to the limited capacity to investigate the DC-tumor interaction in ....Adoptively transferred dendritic cells (DC) loaded with tumor associated antigen (TAA) have been shown to induce anti-tumor immunity in animal models; however, their therapeutic efficacy in cancer patients has not been established. Protective immunity has failed in the tumor-bearing host and the ability of human DC to induce anti-tumor responses in the abnormal environment of the cancer patient requires further investigation. Due to the limited capacity to investigate the DC-tumor interaction in patients, humanized animal models containing human DC and tumor provide an opportunity to obtain important new information. We propose to develop multiple myeloma (MM) as a human tumor in our humanized (hu)NOD-SCID model containing human DC, and to use this in vivo MM-huNOD-SCID model to restore immunity by correcting the human DC-tumor interaction.This knowledge will act as a fast track to select and design a new (simplified) DC-based immunotherapy to treat cancer patients and will be translated directly into our MM clinical trials program, potentially by targeting human DC based on CD205 recognition.Read moreRead less
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
The Role Of The Dendritic Cell Surface Molecule Clec9A In Dendritic Cell Subset Function And Dead Cell Recognition
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Dendritic cells (DC) are sentinels of the immune system. DC monitor the environment and regulate tolerance to self versus immunity to dangerous material. Different types of DC perform different jobs. We have identified a new surface molecule, Clec9A, on some mouse and human DC. We will investigate the function of Clec9A in the immune response. We will also use Clec9A to help unite mouse and human DC biology, since until now there have been few useful marker molecules common to both species.