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Research Topic : T cell response
Scheme : NHMRC Development Grants
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  • Funded Activity

    Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $197,750.00
    Summary
    The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
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    Development And Prototype Manufacture Of A High-throughput CD4 T-cell Test For Management Of HIV/AIDS Infections

    Funder
    National Health and Medical Research Council
    Funding Amount
    $163,150.00
    Summary
    CD4 T-cells are the target of HIV-AIDS infection, and monitoring of HIV-infected patients for these cells is an essential part of disease management. Current CD4 testing methods rely on expensive equipment and reagents and high levels of training, or else they have low throughput that limits their use. This project will develop a standard laboratory assay method for testing CD4 T-cells, increasing the access of patients to CD4 testing, and to HIV therapy, worldwide.
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    Funded Activity

    Development Of An Assay To Distinguish Between Recent And Established HIV-1 Infection

    Funder
    National Health and Medical Research Council
    Funding Amount
    $192,500.00
    Summary
    We have discovered a marker of recent HIV infection. Further refinement of this assay and fully evaluating it on samples from individuals infected with different subtypes of the virus will result in an HIV incidence assay ready for commercialisation. An assay capable of distinguishing between recently acquired and established HIV infection would be most valuable in establishing the incidence of infection for epidemiological surveys, to clearly identify new infections following vaccine trials and .... We have discovered a marker of recent HIV infection. Further refinement of this assay and fully evaluating it on samples from individuals infected with different subtypes of the virus will result in an HIV incidence assay ready for commercialisation. An assay capable of distinguishing between recently acquired and established HIV infection would be most valuable in establishing the incidence of infection for epidemiological surveys, to clearly identify new infections following vaccine trials and identify HIV infection as opposed to transfer of maternal antibodies in new born infants.
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    Development Of New Antivirals.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $433,465.00
    Summary
    Despite recent advances in therapeutic options, chronic viral infections, including infection with hepatitis C virus and hepatitis B virus, continue to be a significant cause of morbidity and mortality in Australia and affecting hundreds of millions of people worldwide. This R&D program aims to develop a cheaper drug formulation that is easier to deliver and more stable for transport to remote areas.
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    Funded Activity

    Rapid, Cost-effective, Diagnosis And Monitoring Of Multiple Sclerosis By Novel Multifocal Evoked Potential Methods

    Funder
    National Health and Medical Research Council
    Funding Amount
    $152,463.00
    Summary
    A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increas .... A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increasing disability of MS. MS only affects about 0.04% of Australians but the early onset of MS, the high cost of medication, and the prolonged period of disability, mean that the cost to Australia is about $2 billion pa. MRI quantifies the inflammatory phase well but is poorly correlated with the debilitating secondary progression. The common treatments for MS target the inflammatory phase but not the causes of secondary progression, which are unknown. Current diagnostic methods mean diagnosis can take years, meaning that patients can be denied treatment for some time. The applicants have published experiments on 50 MS patients and 27 normal subjects using a variant of the new method. Not only has it shown high diagnostic accuracy, but the new method seems to provide data on the progressive phase, suggesting strongly that it is complementary to MRI. The new method is also much cheaper to set up and run than MRI and so could provide cost-effective means for monitoring patient condition and testing new drugs that are effective against the progressive phase. The applicants have considerable experience commercialising diagnostic technologies, and are currently working with an Australian company developing new diagnostic hardware. That hardware has been adapted to perform the presently proposed experiments. Overall it is reasonable to assume that positive outcomes will be translated into economic and health benefits for Australians.
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    Funded Activity

    Production Of A Novel Humanised Anti Dendritic Cell Therapeutic Antibody For Graft Versus Host Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $202,500.00
    Summary
    A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be use .... A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be useful for the prevention of rejection in solid organ transplantation. If successful, it will selectively control graft versus host disease, without compromising the essential anti-viral immunity and desired anti-leukemia activity of the graft.
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    Funded Activity

    Phase 1 Clinical Trial Of Autologous Dendritic Cells To Induce Antigen-specific Tolerance

    Funder
    National Health and Medical Research Council
    Funding Amount
    $165,125.00
    Summary
    We have previously generated modified dendritic cells in mice with the ability to suppress immune responses once they have started. This project will develop the dendritic cell vaccine as a platform technology for human clinical use. We aim to demonstrate, in a phase I clinical trial, the capacity of modified human autologous dendritic cells to suppress the immune response to a model antigen in a group of healthy volunteers and a group of patients with rheumatoid arthritis taking drugs for their .... We have previously generated modified dendritic cells in mice with the ability to suppress immune responses once they have started. This project will develop the dendritic cell vaccine as a platform technology for human clinical use. We aim to demonstrate, in a phase I clinical trial, the capacity of modified human autologous dendritic cells to suppress the immune response to a model antigen in a group of healthy volunteers and a group of patients with rheumatoid arthritis taking drugs for their disease
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    Funded Activity

    Development Of Novel Anti-cancer And Immunosuppressive Drugs Derived From Pineapple Stems

    Funder
    National Health and Medical Research Council
    Funding Amount
    $469,500.00
    Summary
    We have discovered two molecules from pineapple stems that show anti-tumour activity in laboratory studies. One molecule, called ananain, blocks a cancer causing protein called Ras, which is defective in approximately 30% of all cancers. The other molecule, called canizain, stimulates the bodies own immune system to target and kill cancer cells. The proposed research seeks to provide proof of concept of the use of ananain and canizain as drug development targets. Once this early proof of princip .... We have discovered two molecules from pineapple stems that show anti-tumour activity in laboratory studies. One molecule, called ananain, blocks a cancer causing protein called Ras, which is defective in approximately 30% of all cancers. The other molecule, called canizain, stimulates the bodies own immune system to target and kill cancer cells. The proposed research seeks to provide proof of concept of the use of ananain and canizain as drug development targets. Once this early proof of principle phase has been completed, we believe that ananain and canizain would be extremely attractive targets for further investment by a major pharmaceutical company.
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    Funded Activity

    Development Of Novel And Selective Anticancer Drugs Derived From Cysteine.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $264,250.00
    Summary
    In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tum .... In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tumour drugs that possess unusually high selectivity in acting on cancer cells without killing normal human cells. Our current proof of concept will be turned into a drug development candidate that will improve our negotiating position with commercial partners.
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    Funded Activity

    Development Of Modified IGF-binding Proteins As Novel Anti-cancer Chemotherapeutics

    Funder
    National Health and Medical Research Council
    Funding Amount
    $77,375.00
    Summary
    We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof .... We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof of concept in vivo in order to attract commercial funding for clinical trials.
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