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
IMMUNOTHERAPY OF MELANOMA WITH DENDRITIC CELL VACCINES
Funder
National Health and Medical Research Council
Funding Amount
$496,980.00
Summary
Melanoma is a skin cancer which continues to increase in incidence in Australia. It is a significant cause of morbidity and mortality because of its tendency to spread from skin to other body sites. It is largely resistant to chemotherapy. Immunological approaches to its treatment hold promise but there is a need to develop more effective vaccines to assist in treatment. Preliminary studies suggest that injection of dendritic cells primed with melanoma antigens induce strong immune responses and ....Melanoma is a skin cancer which continues to increase in incidence in Australia. It is a significant cause of morbidity and mortality because of its tendency to spread from skin to other body sites. It is largely resistant to chemotherapy. Immunological approaches to its treatment hold promise but there is a need to develop more effective vaccines to assist in treatment. Preliminary studies suggest that injection of dendritic cells primed with melanoma antigens induce strong immune responses and regression of melanoma. If this can be confirmed it will represent a significant advance in treatment of the disease. The studies in the proposal are to investigate whether a new form of treatment based on immunisation with dendritic cells sensitised with tumour antigens will prove to be more effective than existing treatments. Dendritic cells are responsible for stimulating immune responses and are grown from the patient's blood. They are then sensitised with tumour antigens and injected into the lymph nodes of the patient. The study will also measure immune responses during the immunisation procedure and assess whether these measures can predict clinical responses in the patient. If the study is successful in its objectives it will assist in development of more effective treatment of melanoma.Read moreRead less
Strategies To Enhance CD4 T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
The immune system is capable of controlling cancer, but frequently does not do so. In this project we will study two factors that compromise anti-cancer immune responses: regulatory T cells, which suppress immune responses, and tolerogenic dendritic cells, which subvert potentially beneficial responses to tumours. By manipulating these factors, we hope to enhance the effectiveness of the immune response against cancer.
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.
Dissecting The Contribution Of CD103+ DC To Priming Of Virus-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Dendritic cells are key regulators of T cell responses against pathogens. This project will examine the contribution and individual function of distinct dendritic cell to the initiation of adaptive immune responses against herpes-simplex virus. Unraveling the delicate interplay between different dendritic cells will provide novel insights into host-pathogen interactions and will have important implications for the development of efficient vaccination strategies.
Identifying Molecular Machinery In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$687,500.00
Summary
Vaccines invoke immune responses that will protect a vaccinated host if they encounter infection. Vaccines can also be deployed to fight cancer. 'Dendritic cells' are the key immune cell responsible for vaccine immunity. While dendritic cells are pivotal to initiating vaccination, little is known about their internal machinery. This research proposal will identify new machinery for dendritic cell vaccine immunity that will serve as therapeutic targets to boost vaccination.