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.Read moreRead less
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 diseaseRead moreRead less
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.Read moreRead less
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.Read moreRead less
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.Read moreRead less
Developing Novel Anti-cancer Agens By High Throughput Chemical Screens For Small Molcules That Modulate The Pro-survival
Funder
National Health and Medical Research Council
Funding Amount
$125,000.00
Summary
Cancer is the second commonest cause of deaths in our community. Unfortunately, treatment often fails or causes unwanted side effects. This proposal seeks to discover and develop a novel class of anti-cancer drugs that act by directly activating programmed cell death (apoptosis). The Bcl-2 proteins are key regulators of cell death and by exploiting knowledge about these prime targets for cancer therapy, we aim to discover drugs that are potentially of considerable medical and commercial value.
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.
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.
Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$157,375.00
Summary
Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown ....Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.Read moreRead less
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.Read moreRead less