Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.
Immunological Mechanisms Of Clinical Responsiveness To Immunotherapy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic c ....There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic cell based vaccine, which uses only cells from the patient to be treated, have each shown a 15% complete, durable, response rate. The remissions have now lasted longer than 3 years in patients otherwise expected to survive less than 1 year, with no serious side effects observed in any of the patients treated. It is likely that part of the success of this treatment is that it targets unique mutations in the patient's own cancer cells, in combination with a powerful immune stimulation from the dendritic cells. In contrast, most carefully run trials, now and in the recent past, have attempted to use more generic targets, common to many patients' cancers. The problem with this approach is likely to be that the patient is tolerant to these, since the targets are common, self proteins. At variance with all previous trials, we found an exact correlation between durable clinical responses and the degree of anti-tumour immunity displayed by the patients T cells. This grant proposal is based on the reasoning that, by studying in depth the characteristics of this successful immune response, in patients with complete, durable, clinical responses, we will be able to make major improvements in the formulation of the therapy.Read moreRead less
Targeting Eph Receptors As Anti-cancer Therapy In Malignant Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$403,639.00
Summary
Malignant gliomas are the commonest form of brain cancer and are characterised by a high degree of morbidity and mortality. Present treatment involves surgery and adjuvant chemoradiotherapy but despite best care the outlook for patients with this disease is poor. The increasing understanding of the biology of glioma offers the prospect of improved therapies. This proposal seeks to investigate a therapy target in this disease in animal models of human malignant glioma.
Inhibiting Tumour Growth By Targeting EphA3 And Disrupting Tumour Stromal And Vascular Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$645,136.00
Summary
Tumours consist of cancer cells, tumour blood vessels and connective tissue, all of which are different to normal tissues. Many of the cells making up tumour vessels and connective tissue are recruited, during initial growth and subsequent spreading of tumours, from the bone marrow. Our research will examine the presence and function of the EphA3 receptor on these cells during tumour development and assess how our anti-EphA3 antibody inhibits tumour growth by targeting stroma and vasculature.
Sensitive Serum Markers For Improved Diagnosis, Monitoring And Screening For Early Detection Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$410,880.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. Mesothelioma is predicted to cost communities hundreds of billions of dollars in compensation. This disease is unusually difficult to diagnose and tends to be already quite advanced by the time patients present to the doctor with symptoms. Unfortunately, treatment options for the majority of patients are limited and most die within a year of diagnosis. ....The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. Mesothelioma is predicted to cost communities hundreds of billions of dollars in compensation. This disease is unusually difficult to diagnose and tends to be already quite advanced by the time patients present to the doctor with symptoms. Unfortunately, treatment options for the majority of patients are limited and most die within a year of diagnosis. In different forms of cancer, levels of certain proteins in the blood can be measured and have been shown to indicate the presence of tumour and in some cases the extent of tumour. These proteins are collectively known as tumour markers. Tumour markers for ovarian, prostate, breast and other cancers are used by doctors to help with the diagnosis of specific cancers, to monitor the patients response to treatment and to give a valuable early warning of remission or relapse. There is no tumour marker currently used for patients with mesothelioma. We have shown in early studies published in the prestigious journal The Lancet that soluble mesothelin related protein (SMRP) is actually elevated in more than 75% of mesothelioma patients and in less than 2% of patients with other cancer and non-cancer lung diseases. In this current project we plan to extend our studies looking at blood levels of SMRP to see if they will help in the care of patients with mesothelioma. So far we have done most of the work in a particular group of patients, but it is vital that the work be extended to other groups with different types and durations of exposure to asbestos and to different areas of the country. As part of that we need to test how stable the molecule is in blood samples, because if it is not very stable it wont be a very pratical test. We also plan to look at some other markers that have been clinically useful in other forms of cancer and we will try to identify new, novel mesothelioma specific markers. This work has the potential to impact on patient care in many centres of the world.Read moreRead less
Evaluation Of Immune Responses To Multiple Tumour Antigens During Tumour Growth
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
It is becoming increasingly clear that cancerous tissues are not hidden from the body's immune system and yet, despite the generation of tumour-specific T cells and antibodies, the immune system does not often destroy solid tumour. Tumours express a large number of potential antigens (molecules in or on cancer cells that can be recognised by the immune system), but T cell responses to tumour antigens may be limited to only a few of these antigens (the dominating ones). These T cells could compet ....It is becoming increasingly clear that cancerous tissues are not hidden from the body's immune system and yet, despite the generation of tumour-specific T cells and antibodies, the immune system does not often destroy solid tumour. Tumours express a large number of potential antigens (molecules in or on cancer cells that can be recognised by the immune system), but T cell responses to tumour antigens may be limited to only a few of these antigens (the dominating ones). These T cells could compete with any other T cells that have been, or are being, generated, preventing their expansion and development into fully functional T cells. If this is true, then tumours will 'escape' immune mediated destruction, as a T cell response to only a few antigens is not likely to be enought to seriously perturb growing tumours. In this grant we will use a well established mouse model of cancer to evaluate immune responses to tumour antigens during tumour growth and try to understand why other potential antigens do not invoke a fully functional immune response. If we are successful, we will have made advances that could lead to new therapies for cancer.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.