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
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.
Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models ....Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models. We now propose to refine this technique in animals in preparation for human clinical trials.Read moreRead less
The DietAdvice Website A New Innovation For Dietitians In Clinical Practice.
Funder
National Health and Medical Research Council
Funding Amount
$140,975.00
Summary
Due to the growing incidence of obesity within Australia, use of computer technology may be a method of targeting these people by increasing access to dietary services. Currently available dietary software in the Australian context only allows analysis of nutrient information. Thus when a dietitian sees a patient they must manually translate food intake to nutrient information, a largely time consuming exercise. DietAdvice is a website that was developed for people to enter in their own food int ....Due to the growing incidence of obesity within Australia, use of computer technology may be a method of targeting these people by increasing access to dietary services. Currently available dietary software in the Australian context only allows analysis of nutrient information. Thus when a dietitian sees a patient they must manually translate food intake to nutrient information, a largely time consuming exercise. DietAdvice is a website that was developed for people to enter in their own food intakes. The food information is sent to a dietitian who develops individualised dietary advice for them. A pilot study of the website has already found it to be feasible in the primary healthcare setting. Tested for 12 months the website was used by 224 patients from GP practices in the Illawarra region of NSW. Approximately 73% of patients were overweight and patients with a high BMI were 1.88 times more likely to use the website in the comfort of their home. Further research about the website however was needed. The research to follow on from the pilot study will aim to refine the DietAdvice website, leading towards its commercialisation for dietitians in clinical practice. The research will be broken into 3 phases. Phase 1 will involve a usability test of the website, assessing the underlying algorithms and testing it with dietitians in private practice. Phase 2 will see volunteers using the website on multiple occasions after being given pre-weighed amounts of food to eat. This will determine how reliable and accurate the information is; and phase 3 will evaluate whether the website is cost effective and if it increases accessibility of health services especially in rural areas. By confirming these attributes there will be a sound basis to commercialise the product.Read moreRead less
Application Of Follistatin To The Resolution Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$330,990.00
Summary
Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing li ....Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing liver cancer, for which current treatments have limited success. We have been studying two proteins, activin and follistatin, both of which are made in the liver. We are interested in activin because it is one of the body's mechanisms to control cell growth, and also seems to stimulate the development of scar tissue. Follistatin is the natural inhibitory substance for activin. It blocks the effects of activin and helps promote cell growth in the liver. We believe that follistatin may also be useful in controlling liver scarring. This process will be studied in animal models of cirrhosis, in the hope that follistatin treatment will reduce the level of liver damage. If successful, this would be important information that would enable us to design treatments applicable to human sufferers of these liver diseases. In another part of the project, we will assess whether activin and follistatin might be useful markers of liver disease. Most patients require a liver biopsy to assess the amount of liver damage, and a simple blood test would be a far easier, less traumatic and cheaper alternative.Read moreRead less
The Development Of Novel, Biofilm-resistant Biomaterials
Funder
National Health and Medical Research Council
Funding Amount
$147,360.00
Summary
Almost all patients who are catheterised long term develop a bacterial infection. Most often, the infection is the result of colonisation of the catheter surface by bacteria. Bacterial colonisation of the surface of biomedical devices represents a significant health threat as such bacterial biofilms are extremely resistant to traditional antibiotic regimens. This project aims to develop novel materials that prevent bacterial colonisation on catheters and other biomedical related devices. Our tec ....Almost all patients who are catheterised long term develop a bacterial infection. Most often, the infection is the result of colonisation of the catheter surface by bacteria. Bacterial colonisation of the surface of biomedical devices represents a significant health threat as such bacterial biofilms are extremely resistant to traditional antibiotic regimens. This project aims to develop novel materials that prevent bacterial colonisation on catheters and other biomedical related devices. Our technology is based on compounds identified from a marine alga that prevent bacterial colonisation of its surface. Similarly, we have shown that these compounds, when coated onto test surfaces, prevent bacterial colonisation of a range of materials.Read moreRead less
Development Of A Serum Based Test For Aggressive Prostate Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$144,950.00
Summary
Prostate cancer is relatively slow growing, taking decades to reach clinical significance. A critical phase in the progression of prostate cancer is the transformation from latent (or dormant) to aggressive tumours; hence the saying that many men die with prostate cancer, rather than of prostate cancer. We aim to develop a test utilising inhibin-activin proteins as surrogate markers of aggressive disease based on our previous studies of a significant correlation between the expression of inhibin ....Prostate cancer is relatively slow growing, taking decades to reach clinical significance. A critical phase in the progression of prostate cancer is the transformation from latent (or dormant) to aggressive tumours; hence the saying that many men die with prostate cancer, rather than of prostate cancer. We aim to develop a test utilising inhibin-activin proteins as surrogate markers of aggressive disease based on our previous studies of a significant correlation between the expression of inhibins in tissues from men with high grade prostate cancer. This study aims to validate the correlation using serum rather than a tissue based assay.Read moreRead less
Development Of A Multiplex Assay For The Identification Of Women At Risk Of Preterm Labour.
Funder
National Health and Medical Research Council
Funding Amount
$202,350.00
Summary
Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days ....Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days of life. The sickest and most premature of these infants require admission to a Neonatal Intensive Care Unit in a tertiary hospital. Aside from the medical implications of premature delivery, there is also a considerable fiscal challenge to society. While treatments for the prevention of labour have improved considerably over the past decade, current screening tests of preterm labour (ie Fetal Fibronectin test) are unreliable and have poor positive predictive values. The principal objective of this project is to develop and deliver a multiplex assay for the prediction and diagnosis of human preterm labour. Through the successful application of our own proteomic discovery programmes using both ovine and human cervico-vaginal fluid samples, we have identified several new protein markers of labour. Having completed this Phase 1 biomarker trial and established proof-of-concept, we are now well positioned to initiate a Phase 2 biomarker trial to determine reliable estimates of assay sensitivity and specificity. This project targets the development of a new diagnostic to meet a recognised market gap. Delivery of such a test will create a new market in pregnancy-based clinical diagnostics and significantly impact on improving health care and quality of life for many preterm babies. Should the project be completed as detailed and mitigate some of the risk of commercial development, it would then be realistic to seek substantial funding from the private sector.Read moreRead less