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Research Topic : tumour necrosis factor (TNF)
Scheme : NHMRC Development Grants
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  • Funded Activity

    Development Of A Highly Potent, Fully Human Anti-GM-CSF Monoclonal Antibody

    Funder
    National Health and Medical Research Council
    Funding Amount
    $334,000.00
    Summary
    Many diseases, such as arthritis, have unwanted inflammatory reactions. Better drugs are needed to control inflammation. A powerful antibody to a significant pro-inflammatory cytokine will be generated; this antibody will be especially designed so that it will not be rejected by patients. Because of its properties it will cost the community less than similar therapeutics. Because inflammatory diseases are common many patients will benefit from our therapeutic.
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    Funded Activity

    Novel Vaccine Formulation For Immunotherapy Of Adenocarcinomas

    Funder
    National Health and Medical Research Council
    Funding Amount
    $178,400.00
    Summary
    We have designed a vaccine based on a unique delivery system. Mice immunised with vaccine were protected from a tumour challenge. We will now design a vacine with a cancer associated protein so that people once immunised can make killer cells. Since humans have different genetic makeup we will produce a vacine which is more effective and will benefit everyone. This vaccine will be more effective than a current vacine in that has yielded promising results in humans.
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    Funded Activity

    Production Of Chimeric Monoclonal Antibodies To Pim1, A Novel Therapeutic Target For Cancer Treatment

    Funder
    National Health and Medical Research Council
    Funding Amount
    $188,850.00
    Summary
    Almost one in six men will develop prostate cancer during his lifetime. Every year, around 10,000 Australian men are diagnosed and more than 2,500 die of the disease, making prostate cancer the second largest cause of male cancer deaths after lung cancer. The research progress made on prostate cancer over the past 10 years has been encouraging. However the five-year survival rate remains low. There is a vital need to develop new methods to treat this disease. An exciting principle has emerged re .... Almost one in six men will develop prostate cancer during his lifetime. Every year, around 10,000 Australian men are diagnosed and more than 2,500 die of the disease, making prostate cancer the second largest cause of male cancer deaths after lung cancer. The research progress made on prostate cancer over the past 10 years has been encouraging. However the five-year survival rate remains low. There is a vital need to develop new methods to treat this disease. An exciting principle has emerged recently with the use of monoclonal antibodies (Mabs) such as Herceptin (a humanised anti-HER2 Mab), which is now being widely used to treat breast cancer. We produced 2 Mabs to Pim1, which significantly inhibited prostate cancer cell growth in mouse prostate cancer model. Pim1 is a novel oncoprotein, a biomarker for the treatment of prostate cancer as it overexpresses in more than 90% of prostate cancer, but not or less expressed in normal prostate, demonstrated by genearrays and immunohistochemical staining. Pim1 plays an important role in cell survival, proliferation and metastasis. Pim1 is a novel target, and the anti-Pim1 Mabs may be of value for the cancer therapy in humans. However, the murine Mab can not be repeatedly used in human because human would produce anti-mouse antibody response, and the murine Mab would be rapidly removed from circulation, which will greatly limit the therapeutic potential of the Mabs. Fortunately, the problem can be overcome by the use of hybrid chimeric antibodies. In this study, we are going to use chimeric technology to humanise the anti-Pim1 Mab and test them in vitro and in mouse model for the preclinical studies. We have had patent to protect our finding, and we are confident to produce mouse-human chimeric Mab for the future clinical trial as we have proper knowledge, techniques. We are also optimic for the future clinical trial as we have the experiences on commercialisation.
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    Funded Activity

    A Novel Non-invasive Diagnostic Imaging Technique Of Metastatic Cancer Using Plasminogen Activator Inhibitor Type 2.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $187,750.00
    Summary
    This project aims to develop a non-invasive tumour diagnostic imaging agent based on a non-toxic protein (PAI2) that we know specifically identifies a critical marker of malignancy. PAI2 will be labelled with commonly used imaging radioisotopes. This novel imaging technique has important potential clinical uses including, determination of the most appropriate treatment for individual patients, assessing the success of such treatments, and a novel non-invasive prognostic indicator of malignancy.
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    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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    Funded Activity

    Pre-clinical Assessment Of Novel Growth Factor Complexes As A Topical Agent In The Treatment Of Deep

    Funder
    National Health and Medical Research Council
    Funding Amount
    $156,870.00
    Summary
    Healing of deep burns, unlike that of superficial injuries, often resolves with scarring. Scarring is reduced with rapid closure of burns. The CIs have discovered and patented novel growth factor complexes that stimulate the growth and migration of keratinocytes, cells derived from skin. Hence these complexes hold therapeutic potential for wounds that require rapid closure such as deep burns. This application will provide pre-clinical, proof-of-principle data to facilitate future patient trials.
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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 Of A Simple Chemical Test For Detecting DNA-interacting Compounds For Medical And

    Funder
    National Health and Medical Research Council
    Funding Amount
    $315,450.00
    Summary
    The project exploits a simple chemical reaction to detect and measure the interaction of compounds with DNA. The test will be useful in the early screening of drug candidates for genotoxicity, identifying new anticancer drugs and also find application in the environmental, cosmetic and food industries. Work will focus on establishing peak conditions for the test, determining the scope of application, testing a panel of control compounds and performing a blind study to provide proof of concept.
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    Funded Activity

    Development Of A Smart Arthroscopy System And Prototype Probe For Joint Tissues

    Funder
    National Health and Medical Research Council
    Funding Amount
    $230,632.00
    Summary
    This project relates to the ever growing use of arthroscopy in the management of joint defects. An innovative probe that will combine all the molecular, microstructural and biomechanical characteristics of joint articular cartialge and bone for the purposes of diagnosis, treatment, treatment-related decisions, comparison of the effectiveness of treament methods and post treatment evaluation will be developed. This system will produce spin-offs for artrhoscopy of other soft tissues and bodies.
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    Funded Activity

    GM-CSF Regulation Of Preimplantation Embryo Development

    Funder
    National Health and Medical Research Council
    Funding Amount
    $481,320.00
    Summary
    Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov .... Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.
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