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 Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Development And Pre-clinical Evaluation Of G-DSF Inhibitors For Inflammatory Joint Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,329.00
Summary
G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in expe ....G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in experimental models of inflammatory joint disease. We propose to develop inhibitors of G-CSF as a novel form of anti-cytokine therapy for inflammatory joint disorders, such as rheumatoid arthritis.Read moreRead less
Development Of A Humanised Antibody For Treatment Of Cancer And Stroke
Funder
National Health and Medical Research Council
Funding Amount
$400,142.00
Summary
The protein PDGF-CC has a critical role in blood vessel development, and is implicated in the development of cancer, and the debilitating consequences of acute stroke. Researchers in the Ludwig Institute for Cancer Research have developed novel anti-PDGF-CC antibodies. The research program proposed will generate data and clinical reagents that will enable a lead candidate anti-PDGF-CC antibody to be commercialised, and ultimately evaluated clinically in cancer and stroke patients.
Development Of Novel Anti-epileptic Drugs Targeting Vesicular Endocytosis
Funder
National Health and Medical Research Council
Funding Amount
$202,950.00
Summary
Our team developed a drug program targeting a novel mechanism for epilepsy treatment, neuronal synaptic vesicle endocytosis. This project will develop the most promising series of drugs. Preclinical development is advanced, lacking only efficacy data across models predictive of the spectrum of human epilepsies to enable candidate selection for clinical trials. The program will advance a totally new concept for the treatment of epilepsy.
Novel System For Non-Invasive Delivery Of Drugs To The Interior Of The Eye
Funder
National Health and Medical Research Council
Funding Amount
$200,213.00
Summary
Age-related macular degeneration (AMD) is the leading cause of visual loss for adults in the developed world. Treatment is now by needle injection into the back of the eye, which is painful for the patient and is costly for the health-care system. Seagull Technology Pty Ltd has developed a non-invasive device for treating the back of the eye without the need for a needle injection. This project will test the new device in animals and then move to a first safety study for human AMD patients.
Development Of Anti-CXCR7 MAbs For The Treatment Of Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$399,998.00
Summary
Fibrosis is a serious biological process that occurs in many disease conditions, including cancer, inflammation and infections. We have produced antibodies to CXCR7, and these antibodies completely inhibit fibrosis in a mouse model. We plan to develop these antibodies in to a suitable drug for human clinical trials.