Improving Efficacy Of Vaccination Against The Gut Pathogen Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$504,000.00
Summary
Helicobacter pylori are bacteria which live in the stomachs of half the World's population, where they are the main cause of two types of stomach cancers, as well as stomach and duodenal ulcers. The development of a vaccine against this organism would have a major impact on these diseases. Unfortunately, while there has been some success in animal models, the results from clinical trials have so far been disappointing. A key issue with vaccines against H. pylori is their poor efficacy, i.e. alth ....Helicobacter pylori are bacteria which live in the stomachs of half the World's population, where they are the main cause of two types of stomach cancers, as well as stomach and duodenal ulcers. The development of a vaccine against this organism would have a major impact on these diseases. Unfortunately, while there has been some success in animal models, the results from clinical trials have so far been disappointing. A key issue with vaccines against H. pylori is their poor efficacy, i.e. although they produce a significant reduction in bacteria numbers in animal models, they do not clear all of the bacteria. The remaining bacteria are sufficient to continue to cause disease. It is currently not understood how these vaccines work in mice, which makes it very difficult to improve their design. An additional problem common to all human vaccines, is the lack of a suitable adjuvant. An adjuvant is a non-specific vaccine component which is required to activate the immune system. Thus, for an effective vaccine it is essential to identify suitable adjuvants which will work against H. pylori and can be used in people. The chief investigator on this project has been working in the H. pylori vaccine field, in both academia and industry, for 8 years. He very recently identified an immunisation regime which greatly increases the effectiveness of vaccination against H. pylori in an animal model. The main aim of this project is to further develop this novel discovery to identify key immune factors that are critical to making an improved vaccine. In addition, the two associate investigators are experts in the area of adjuvants for human vaccines, and will help to test new vaccine systems in the H. pylori model. If successful, this project will generate highly significant data that will strongly contribute towards the design of an improved vaccine strategy against H. pylori in people.Read moreRead less
Protease-activated Receptor-1 (PAR-1) And Regulation Of Helicobacter Pylori Induced Mucosal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$478,090.00
Summary
Helicobacter pylori infections cause chronic gastritis which in some people results in stomach cancer or ulcers. We have identified a novel host factor, PAR-1, important for preventing this inflammation. We will use mice to identify how this molecule protects against gastritis and samples from patients to examine its importance in human disease. This will help explain why these diseases develop in some people but not others and perhaps allow identification of those at risk of developing disease.
Biomarker-driven Applications Of Immunotherapy In Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$189,384.00
Summary
Immunotherapy is a new treatment strategy that works in many different lymphoma types but there is no successful method of predicting response or selecting patients. I aim to explore use of immunotherapy in 3 key lymphoma subtypes to identify new techniques for predicting which patients respond to treatment through prospective biomarker research using novel techniques. These aims will be achieved through a series of clinical trials of immunotherapy in lymphoma all with a biomarker research focus
The Role Of CD30 Overexpression In CD30-positive Non-Hodgkins Lymphomas
Funder
National Health and Medical Research Council
Funding Amount
$457,242.00
Summary
The CD30 molecule sits on the surface of normal blood cells, but in a type of cancer called Lymphoma, CD30 concentration is high. The level of expression of CD30 may determine if the cancer cell is killed by the normal defense mechanisms or is able to grow uncontrollably. We are studying the control elements of the CD30 gene to understand how control is lost when the cell becomes cancerous. This knowledge may lead to therapeutic strategies to control lymphoma.
EBV-specific T Cells As Therapy For Relapsed - Refractory EBV-positive Lymphomas
Funder
National Health and Medical Research Council
Funding Amount
$324,397.00
Summary
The presence of Epstein-Barr virus (EBV) withiin EBV-positive malignant lymphoma cases provides a potential target for adoptive immunotherapy. Previous studies have established that adoptive immunotherapy for certain subtypes of lymphoma with EBV-specific killer T cells can lead to remission of disease. The objective of this study is to examine whether a similar strategy but using an enhanced methodology can be applied for the treatment of a range of relapsed-refractory EBV-positive lymphomas.
A Transcription Factor Network Constraining The Development Of B Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
B cell leukemias are relatively common, often aggressive hematopoietic malignancies and their cause is unknown in many cases. We have found that deficiencies in several transcription factors that normally control B cell differentiation cause B cell leukemias at a high frequency. We wish to identify the key pathways that are regulated by these factors and, in normal cells, prevent leukemic transformation. This will help to identify potential targets for therapeutic intervention.
A Prospective Single Arm Trial Of Involved-field Radiotherapy For Stage I-II Low Grade Nongastric Marginal Zone Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$363,869.00
Summary
This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT ly ....This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT lymphomas, but the association has never been prospectively studied. Chlamydia Psittaci infection can cause MALT lymphoma in the orbit. The management of localised MZL outside the stomach is controversial and there have been no large prospective studies of any of the commonly-used treatments (radiotherapy, chemotherapy, surgery). No prospective studies have looked at the role of infection with Helicobacter pylori or the role of autoantibodies in these diseases. Radiotherapy is the best-characterised therapy in the literature and appears to have a high cure rate with low toxicity. The disease seems exquisitely radiosensitive. Management of localised MZL in Australia can be ad hoc and we have often seen patients who have undergone unnecessary mutilating surgery or ineffective chemotherapy. It has been reported that localised non-gastric MZL (stage I and II) can be cured with radiotherapy in a high percentage of patients (usually >70%) in retrospective studies from large centres such as Princess Margaret Hospital in Toronto. Workers from that centre will participate in this study. This study will: Prospectively report efficacy and toxicity for radiotherapy in MZL for the first time Definitively document Helicobacter Pylori status in all cases and Chlamydia status in orbital cases Provide a gold standard against which to compare new therapies This study won the award for the most highly supported study in its year at the TROG annual scientific meeting.Read moreRead less
Adult non-Hodgkin?s lymphoma (NHL) is one of the most rapidly increasing cancers of recent times. The rise has occurred worldwide in men and women of all ages. The reason for most of the rise is unknown. It has recently been proposed that part of the upsurge may be due to increases in sun exposure which have occurred during the same period. There is some indirect evidence to support this hypothesis. For example, the rate of occurrence of NHL is higher closer to the equator in Australia than it i ....Adult non-Hodgkin?s lymphoma (NHL) is one of the most rapidly increasing cancers of recent times. The rise has occurred worldwide in men and women of all ages. The reason for most of the rise is unknown. It has recently been proposed that part of the upsurge may be due to increases in sun exposure which have occurred during the same period. There is some indirect evidence to support this hypothesis. For example, the rate of occurrence of NHL is higher closer to the equator in Australia than it is in England and Wales, and NHL is diagnosed more frequently among British migrants to Victoria than it is in their homeland. The sunlight hypothesis will be tested by comparing the pattern of sun exposure in Tasmanians diagnosed with NHL during the years 1998-2001 and in a sample of Tasmanians without the disease. tasmania has been chosen because levels of ultraviolet (UV) radiation are low there in all but the summer months, when it approaches the levels of Brisbane, Sydney and Melbourne. There is therefore a greater difference in UV exposure between the most exposed and the least exposed in Tasmania, making it an ideal location to test the hypothesis. The link between NHL and a measure of melanin pigmentation in the skin will also be studied. The incidence of NHL is higher in lighter-skinned ethnic groups than it is in darker-skinned people living at the same latitude, but it is not known whether risk varies within Caucasian populations. A new measure of melanin in the skin, developed at the Menzies Centre for Population Health Research in Hobart, will better allow the effects of skin colour to be studied.Read moreRead less