Targeted Alpha Therapy For Metastatic Breast Cancer Using Alpha-Herceptin
Funder
National Health and Medical Research Council
Funding Amount
$332,420.00
Summary
The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of H ....The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of HIV-1 to provide universal coverage of the major HIV-1 strains for a global population. The synthetic systematically designed HIV-1 vaccine will be delivered using our newly developed prime-boost immunisation regime that induces particularly high levels of cell-mediated immunity.Read moreRead less
Development Of Anti-CXCR2 Monoclonal Antibodies For Tumour Therapy
Funder
National Health and Medical Research Council
Funding Amount
$174,867.00
Summary
New therapies to treat cancers and inflammatory diseases are urgently required. Our aim is to develop a new treatment for cancer and inflammation, by blocking the chemokine receptor CXCR2 which is central to angiogenesis (blood vessel growth) and inflammation. We have produced a highly effective monoclonal antibody (mAb) inhibitor of CXCR2, that is suitable for preclinical and clinical development. The project aims to examine the efficacy of this mAb in mouse tumour models and inflammation.
The Development Of Store Operated Calcium Channel Monoclonal Antibody Inhibitors As A Therapeutic Option For Breast Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$230,753.00
Summary
Despite recent advances in the treatment of breast cancer, a significant proportion of women with this disease receive little benefit from currently available treatments and die from breast cancer. Hence, new therapies for the breast cancers with the poorest prognosis are needed. This grant exploits our earlier finding that a specific calcium channel is a likely therapeutic target for breast cancer. Funding from this grant will be used to develop an inhibitory monoclonal antibody to this target.
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 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.
Targeted Alpha Therapy: Development Of A New Treatment For Metastatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$394,400.00
Summary
Breast cancer is the most commonly diagnosed, malignant cancer in women and prostate cancer is the most common non-life style related cancer in men. In spite of the most aggressive therapy, a significant percentage of men and women die of secondary disease (metastases) which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long term survival is uncertain. Targeted alpha therapy (TAT) is a new cance ....Breast cancer is the most commonly diagnosed, malignant cancer in women and prostate cancer is the most common non-life style related cancer in men. In spite of the most aggressive therapy, a significant percentage of men and women die of secondary disease (metastases) which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long term survival is uncertain. Targeted alpha therapy (TAT) is a new cancer treatment that we are developing in mouse models of human breast and prostate cancer. With TAT we are exploiting the fact that aggressive breast and prostate cancer cells, but not normal cells, express a particular tissue-barrier degrading protein system (uPA) which is specifically recognised by a natural inhibitor protein (PAI2). This protein inhibitor is labeled with a highly effective cell killing agent, a radioisotope that emits high energy alpha particles with a short range of only a few cell diameters . The alpha-labeled PAI2 selectively kills cancer cells at their most malignant stage by targeting the uPA system on these cells. Another benefit of TAT is that little radiation damage occurs to nearby or distant normal cells. Thus side-effects would be minimised. The outcome of our research to date has been to show the potential of our unique TAT approach as a possible new therapy for breast and prostate cancer. This therapy may well prove beneficial for other cancers. Further safety evaluations studies in mice will be followed by a dose tolerance clinical trial in humans. We expect to be able to show that our TAT will regress breast and prostate cancer tumours without complications in mice. The human trials will show the tolerance limits to TAT. If successful, TAT could provide the basis for a major change in prognosis and quality of life of breast and prostate cancer patients.Read moreRead less
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.
In Vitro And In Vivo Assessment Of The Funhaler -an Innovative Therapeutic Device For Children
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler ....Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler incorporates a spinning toy attached to the outside of the spacer. The toy is activated when the patient breathes through the spacer. The device has been designed to encourage children to co-operate when their asthma therapy is being delivered. The Funhaler is currently in the late development stage. We propose, firstly, to carry out in vitro assessments of drug delivery from the Funhaler compared to the two most widely available small volume spacers: the Aerochamber Plus (Trudell, Canada) and the Breath-A-Tech (Scott-Dibben, Australia). These assessments will be carried out to meet the standards of regulatory bodies worldwide (including the FDA). Secondly, we propose to perform extensive in vivo studie: filter studies to assess drug delivery to the patient; deposition studies to measure drug deposition in the lungs; and a pilot clinical trial to assess the efficacy of the device during medium to long-term use in children aged 2-8 years.Read moreRead less
External Therapeutic Device To Support Rehabilitation Of The Hand Following Trauma Or Surgery
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and ....The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and tendon sheath adhesions or non-functional scar tissue formation, continuous passive motion (CPM) is often indicated. Additionally, for people with reduced mobility of the hand due to upper limb paralysis, such as those with cervical spinal cord injury, stroke, cerebral palsy or peripheral nerve injury, disregard for management of the maintenance of the joint range of motion of the effected hand will result in contracture and limited joint range of motion. Such syndromes will reduce hand function, which is already limited by paralysis, and will negatively affect potential outcomes for aggressive rehabilitation techniques, such as tendon transfer surgery and functional neuromuscular stimulation. Therefore, in such cases, CPM is also indicated. Current devices applying CPM have shown to be effective in minimising the syndromes indicated above and these results are summarised in the Background and Research Plan attached to this proposal. Unfortunately, the use of such devices is not always prescribed by clinicians. This is due, mainly, to the limitations of these devices that are in the marketplace. These limitations include lack of secure finger placement, lack of portability, the inability to provide specialised therapy to specific joints and inflexible programming. This proposal introduces an improved device to be developed and these improvements form the proposal aims below. Given such an improved device, which can overcome many of the problems with current CPM machines, it is likely that that the clinical application of CPM will achieve the greater degree of prescription and application in hand rehabilitation. These improvements should overcome the clinical reticence to use these devices and restore a balance by increasing their use to the level that the scientific literature indicates they should have. The overall aim of the proposal is to take the device to a stage where it is ready for clinical trial.Read moreRead less