Radioimmunotherapy is an experimental method of cancer treatment, involving the use of radioactive isotopes, which are targeted to tumour cells using specific molecules as carriers. These carriers are known as anti-tumour antibodies, and they bind specifically to tumour cells. Recent advances in molecular biology and in the understanding of the nature of tumour cells has resulted in the development of improved anti-tumour antibodies, and such improvements can be expected to continue. However, th ....Radioimmunotherapy is an experimental method of cancer treatment, involving the use of radioactive isotopes, which are targeted to tumour cells using specific molecules as carriers. These carriers are known as anti-tumour antibodies, and they bind specifically to tumour cells. Recent advances in molecular biology and in the understanding of the nature of tumour cells has resulted in the development of improved anti-tumour antibodies, and such improvements can be expected to continue. However, this project is concerned not with the tumour targeting aspect of radioimmunotherapy, but rather with the payload or cytotoxic mechanism, in which the radiation damage is focused on the DNA of the cell. In summary, the project explores a new approach in cancer radioimmunotherapy. This approach will be evaluated firstly in cultures of tumour cells and then in mice bearing transplanted tumours. If successful this project will result in the development of a new cell kill technology that can be combined with different anti-tumour antibodies.Read moreRead less
Regulation Of Mitogenic Signalling Via The Gab2 Docking Protein
Funder
National Health and Medical Research Council
Funding Amount
$141,750.00
Summary
Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. F ....Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. Furthermore, we have identified that another protein, termed PKB, can 'switch off' signalling by Gab2, and that deregulated signalling by Gab2 can make cells cancerous. The aim of this project is to characterize how PKB regulates Gab2, and to investigate whether this mechanism is impaired in human cancers, leading to enhanced Gab2 signalling. The research will provide important information regarding how growth factor signals are transmitted inside cells, and may identify a new cancer-causing gene.Read moreRead less
Targeting 124I To The DNA Of Tumours For PET Imaging And Auger-Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$787,000.00
Summary
The aim of this project is to develop a new method of targeting radioactivity to tumours, for detection and treatment, using a radioactive element (iodine-124). Iodine-124 emits a form of radiation called positrons, detected by a new imaging technique - Positron Emission Tomography (PET). Therefore, tumours labelled with iodine-124 can be imaged by PET. Also, iodine-124 is amongst a class of radioactive atoms (called Auger-emitters) that emit a shower of very low energy electrons. This intense f ....The aim of this project is to develop a new method of targeting radioactivity to tumours, for detection and treatment, using a radioactive element (iodine-124). Iodine-124 emits a form of radiation called positrons, detected by a new imaging technique - Positron Emission Tomography (PET). Therefore, tumours labelled with iodine-124 can be imaged by PET. Also, iodine-124 is amongst a class of radioactive atoms (called Auger-emitters) that emit a shower of very low energy electrons. This intense focus of radiation damage, can be exploited to kill cancer cells by inflicting lethal DNA damage. To bring the iodine-124 close to the DNA molecule, we will attach it to a DNA-binding drug linked to a tumour-seeking protein, such as an anti-tumour antibody. After injection of the radioactive drug-protein cocktail, PET imaging will be used to assess the extent of tumour targeting, to enable calculation of the amount of cocktail required for successful tumour treatment by further injections. There are some situations where tumour imaging needs to be non-damaging, such as in using PET imaging to assess the success of surgical removal of a tumour. Therefore, we will design an alternative version of the iodine-124-labelled DNA- binding drug with the radioactive atom in a location that will minimise DNA damage from radioactive decay. In this imaging-only scenario, the Auger-emission feature is suppressed whilst still exploiting positron-emission for imaging. The stability of radioactive atoms varies widely, and the half-life of iodine-124 (about four days) is an ideal compromise for imaging and treatment. By contrast, the utility of the most commonly used isotope for PET imaging, fluorine-18, is limited by its half-life of only a few hours. The PET Centre at PeterMac will soon produce iodine-124, joining one of only a few centres throughout the world. Peter Mac has recently lodged a patent application for the technology to be developed in this project.Read moreRead less
Colorectal Cancer - Molecular Basis To Targeted Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$19,818,386.00
Summary
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Last year an estimated 3.1 million people died of AIDS (source: UNAIDS, Dec 2002) equivalent to the number killed by tuberculosis and malaria combined. AIDS-related opportunistic infections (OIs) are the main cause of death for AIDS patients, especially in resource constrained countries where access to antiretroviral and antibiotic therapy is limited. Attempts to limit the epidemic have failed and new foci have emerged in Eastern Europe, Central Asia and, of particular relevance for us, South Ea ....Last year an estimated 3.1 million people died of AIDS (source: UNAIDS, Dec 2002) equivalent to the number killed by tuberculosis and malaria combined. AIDS-related opportunistic infections (OIs) are the main cause of death for AIDS patients, especially in resource constrained countries where access to antiretroviral and antibiotic therapy is limited. Attempts to limit the epidemic have failed and new foci have emerged in Eastern Europe, Central Asia and, of particular relevance for us, South East Asia, underlining the fact that safe and effective treatment for AIDS-related OIs will be a global health priority for the foreseeable future. People with healthy immune systems do not get OIs since the germs that cause such infections are efficiently ingested and subsequently destroyed by cells called macrophages. We have discovered that the virus that causes AIDS, HIV-1, interferes with the ability of macrophages to ingest opportunistic pathogens by the 2 most important mechanisms used for this purpose. We believe that this is the direct cause for the susceptibility of AIDS patients to many of the opportunistic pathogens that cause their OIs. The purpose of this grant will be to understand the biochemical basis underlying these 2 defects in macrophage function. This will help in the design of safe, adjunctive therapies aimed at improving macrophage function and reducing the risk of HIV-infected individuals developing AIDS-related OIs.Read moreRead less