An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.
Immunoregulatory Immune Responses To A Peripherally Presented Tumour Antigen
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
Tumours express proteins which the body can recognise as foreign. However, the recognition process often goes wrong, leaving the body's defences against infection unable to respond to the tumour. This lack of response may become permanent, and the tumour may then be protected by the immune system. We have a model system, based on cervical cancer, in which we can determine the reasons why tumour tolerance can occur, and explore ways of overcoming the tolerance
Evaluation Of Immune Responses To Multiple Tumour Antigens During Tumour Growth
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
It is becoming increasingly clear that cancerous tissues are not hidden from the body's immune system and yet, despite the generation of tumour-specific T cells and antibodies, the immune system does not often destroy solid tumour. Tumours express a large number of potential antigens (molecules in or on cancer cells that can be recognised by the immune system), but T cell responses to tumour antigens may be limited to only a few of these antigens (the dominating ones). These T cells could compet ....It is becoming increasingly clear that cancerous tissues are not hidden from the body's immune system and yet, despite the generation of tumour-specific T cells and antibodies, the immune system does not often destroy solid tumour. Tumours express a large number of potential antigens (molecules in or on cancer cells that can be recognised by the immune system), but T cell responses to tumour antigens may be limited to only a few of these antigens (the dominating ones). These T cells could compete with any other T cells that have been, or are being, generated, preventing their expansion and development into fully functional T cells. If this is true, then tumours will 'escape' immune mediated destruction, as a T cell response to only a few antigens is not likely to be enought to seriously perturb growing tumours. In this grant we will use a well established mouse model of cancer to evaluate immune responses to tumour antigens during tumour growth and try to understand why other potential antigens do not invoke a fully functional immune response. If we are successful, we will have made advances that could lead to new therapies for cancer.Read moreRead less
Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
The Role Of CD4+ T Cells In The Tumour Killing By CD8+ Memory T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wi ....It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wish to study the mechanism of how CD8+ memory T cells get activated to cancer killer cells by the CD4+ T helper cells. This information will help us to design better immunotherapies for cancer patients.Read moreRead less
EBV-specific T Cells As Therapy For Relapsed - Refractory EBV-positive Lymphomas
Funder
National Health and Medical Research Council
Funding Amount
$324,397.00
Summary
The presence of Epstein-Barr virus (EBV) withiin EBV-positive malignant lymphoma cases provides a potential target for adoptive immunotherapy. Previous studies have established that adoptive immunotherapy for certain subtypes of lymphoma with EBV-specific killer T cells can lead to remission of disease. The objective of this study is to examine whether a similar strategy but using an enhanced methodology can be applied for the treatment of a range of relapsed-refractory EBV-positive lymphomas.
Sunscreen Immune Protection Factor Prediction Of Inhibition Of Anti-tumour Immunity And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$186,372.00
Summary
Despite sunscreens having been used in Australia for more than 25 years the incidence of skin cancer continues to increase. This is partly due to the long lag time in developing a skin cancer, so that the current incidence reflects sun exposure patterns of many years ago. However this is also partly due to sunscreens not being as effective at preventing skin cancer as they are at preventing sunburn. The ultraviolet wavelengths found in sunlight are the prime cause of skin cancer. Australians are ....Despite sunscreens having been used in Australia for more than 25 years the incidence of skin cancer continues to increase. This is partly due to the long lag time in developing a skin cancer, so that the current incidence reflects sun exposure patterns of many years ago. However this is also partly due to sunscreens not being as effective at preventing skin cancer as they are at preventing sunburn. The ultraviolet wavelengths found in sunlight are the prime cause of skin cancer. Australians are exposed to high levels of sunlight, and consequently 66% of Australians develop skin cancer throughout their lifetime. For this reason, Australia has been dubbed the Skin Cancer Capital of the World. To reduce the incidence of skin cancer in Australia, it is recommended that individuals use sunscreens. The means of assessing the effectiveness of sunscreens is based on an SPF system, which measures the ability of sunscreens to prevent sunburn (erythema). However sunburn is induced by particular ultraviolet wavelengths, and may not be as important for skin cancer assessment as other damaging effects of sunlight, such as immunosuppression and genetic mutations. Sunscreens should be tested for protection from immunosuppression as well as sunburn, as this would aid the development of better sunscreens. We have developed the technology to measure protection of the immune system, and intend to investigate the usefulness of this new sunscreen test.Read moreRead less
Development Of Cancer Immunotherapy Using Gene-engineered T Cells In A Self-antigen Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$428,602.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells.