Integrating Conventional Mesothelioma Therapies With Immuno- And Gene-therapies
Funder
National Health and Medical Research Council
Funding Amount
$804,916.00
Summary
Asbestos-induces cancers are some of the most aggressive cancers know to medicine. Unfortunately, treatments are not very effective and it is unusual for these cancers to be cured, particularly mesothelioma. Because recent scientific studies have suggested that combinations of therapy which include immunotherapy, ie treatments aimed at stimulating the bodies anti-cancer immune responses to attack the cancer, can be effective, we plan to develop this work in order to determine exactly which combi ....Asbestos-induces cancers are some of the most aggressive cancers know to medicine. Unfortunately, treatments are not very effective and it is unusual for these cancers to be cured, particularly mesothelioma. Because recent scientific studies have suggested that combinations of therapy which include immunotherapy, ie treatments aimed at stimulating the bodies anti-cancer immune responses to attack the cancer, can be effective, we plan to develop this work in order to determine exactly which combinations are likely to be the most effective and therefore the most suitable for clinical trial in patients.Read moreRead less
Epidemiology And Community Consequences Of Asbestos Exposure In WA
Funder
National Health and Medical Research Council
Funding Amount
$879,876.00
Summary
We aim to explore the impact of asbestos exposure on the health of individuals using the Wittenoom workers and residents cohort studies and the Australian community with the formation of a new community based cohort study. Using data from the Wittenoom workers and residents studies, we will examine the impact of asbestos exposure on women�s health which has not been looked at before. We will examine if asbestos exposure affects psychosocial health and determine if long term supplementation with ....We aim to explore the impact of asbestos exposure on the health of individuals using the Wittenoom workers and residents cohort studies and the Australian community with the formation of a new community based cohort study. Using data from the Wittenoom workers and residents studies, we will examine the impact of asbestos exposure on women�s health which has not been looked at before. We will examine if asbestos exposure affects psychosocial health and determine if long term supplementation with Vitamin A for cancer prevention results in an increased risk of bone fractures. We will also examine the genetic susceptibility of asbestos related diseases in these cohorts, and create and validate an algorithm to derive measures of fibre counts from occupational histories. Earlier projections of mesothelioma in the general community have been based on extrapolations from disease incidence in the past. We intend collecting data on a new community based cohort, to examine the distribution of asbestos in the community in order to predict future cases of asbestos related disease and the perception, beliefs and knowledge that exists in the community of its potential health effects. With this new knowledge we will devise an intervention program with the aim of preventing future cases of asbestos related disease. As part of this process we will use a multimedia website as an information hub. This will allow us to experiment with the use of creative media to present personal and community experiences of living with asbestos and present scientific research and public health messages.Read moreRead less
Cancers can spread to the lung causing fluid build-up and requires drainages in hospital that are painful and costly. Surgery is previously seen as the definitive option to stop fluid forming, but is invasive with complications. Indwelling pleural catheter (IPC) is a novel implanted device inside the chest that allows patients to drain fluid at home. AMPLE Trial-3 is the first multicenter randomized clinical trial to compare surgery vs IPC to provide fluid control and improve quality of life.
Conditionally Replicative Adenoviruses For Mesothelioma Therapy
Funder
National Health and Medical Research Council
Funding Amount
$260,600.00
Summary
Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy ....Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy relies on selective viral replication in (and therefore death of) tumour cells but not normal cells. In principle, mesothelioma is an attractive target for this therapeutic approach owing to its propensity to remain localised to the pleural space until late in the disease. However, for any CRAd strategy to succeed, viral replication must be limited to the tumour cells so as not to cause unnecessary toxicity to normal tissues. This level of specificity can potentially be achieved by using cell-specific promoters to control the expression of viral genes essential for replication. To date however, there have been no reports evaluating candidate mesothelioma-specific promoters in adenoviral vectors. Furthermore, other issues such as tumour a lack of viral receptors or tumour-associated fibrosis could limit viral spread through a mesothelioma mass and reduce the efficacy of the approach. In this proposal we will contruct and test CRAds which are controlled by promoters which we believe will be highly active in mesothelioma, but very poorly active in other tissues. We will test the ability of these new agents to kill mesothelioma cells in tissue culture, in pieces of mesothelioma tumours removed from patients, and in animal models. If successful, this approach could offer new hope for mesothelioma patients.Read moreRead less
Role Of FLT PET In Malignant Pleural Mesothelioma - Prediction Of Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$93,639.00
Summary
Mesothelioma is a cancer of the lining of the lung. Chemotherapy is often used to treat patients in order to reduce their symptoms and to improve quality and length of life. Not all patients however benefit from chemotherapy, and most patients will experience some side-effects. Currently CT scans are used to assess response to chemotherapy, however the way that mesothelioma grows makes measuring response difficult. CT scans also are not very sensitive in detecting response early - often 3 or 4 c ....Mesothelioma is a cancer of the lining of the lung. Chemotherapy is often used to treat patients in order to reduce their symptoms and to improve quality and length of life. Not all patients however benefit from chemotherapy, and most patients will experience some side-effects. Currently CT scans are used to assess response to chemotherapy, however the way that mesothelioma grows makes measuring response difficult. CT scans also are not very sensitive in detecting response early - often 3 or 4 cycles of treatment (3-4 months) are required before benefit is seen. A test that could predict which patients were benefiting after only 1 cycle (3-4 weeks) of chemotherapy would be a great advantage, and may spare some patients unnecessary and potentially toxic treatment. Fluorothymidine (FLT) is a radioactive tracer that, after injection into a vein, is taken up by dividing cells. Tumour cells usually divide more actively than surrounding normal cells, and therefore when a positron emission tomography (PET) scan is performed it will demonstrate the tumour as a 'hot spot'. The amount of FLT uptake into the tumour depends on how much DNA synthesis (active cell division) is occurring. After chemotherapy, if the tumour responds it would be expected that the amount of FLT in the tumour will reduce. This can be assessed by repeating the FLT PET scan after the first cycle of chemotherapy. This study aims to assess the ability of the change in FLT uptake in mesothelioma after 1 cycle of chemotherapy to predict response, as measured on CT scans, and patient outcomes such as quality of life and survival. It is hoped that if successful this type of scan may improve patient care by selecting those who are likely to benefit from chemotherapy early and avoid unnecessary toxicity to patients who will not benefit from the treatment.Read moreRead less
Optimising Regulatory T Cell Depletion In Combination With Chemotherapy For Enhanced Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$264,816.00
Summary
The drug cyclophosphamide helps the immune system attack cancer by decreasing the number of immune cells that suppress an immune response to cancer ('Regulatory T cells'). This project combines standard chemotherapy with the drug cyclophosphamide in people with mesothelioma and lung cancer. The aim of the project is to find the dose of cyclophosphamide that maximally decreases Regulatory T cells in each patient, and determine the effect of this on anti-tumour immunity and response to treatment.
Inhaling asbestos fibres causes cancer (both mesothelioma and lung cancer). These are related to the amount of asbestos inhaled. This study will look at lung tissue removed from people for other medical reasons to see if those at high risk (e.g. construction workers) have benefited from the laws restricting asbestos use. We hope to predict rates of these cancers in the future from these results, based on the numbers of fibres seen in the lungs.
The Impact Of Therapy On T-cell Recognition Of Mutated Tumour Neo-antigens
Funder
National Health and Medical Research Council
Funding Amount
$1,126,685.00
Summary
Cancer is caused by mutations which should be 'seen' and destroyed by the patients immune cells, similar to how immune cells protect us against viruses. But they don't. This grant will study how current cancer treatments help the immune cells 'see' these mutations. We will undertake these studies in the important cancers lung cancer and mesothelioma.