A Dendritic Cell Subset Targeting Approach For Defining Immune Function And Tailoring Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$692,753.00
Summary
Dendritic cells are important sentinel cells of the immune system that orchestrate our immune responses against invading pathogens. There are different types of dendritic cells and they perform different jobs. We have a series of antibodies that can recognise markers on the surface of different dendritic cells populations. We can use these antibodies as homing devices to deliver foreign material to individual dendritic cell subpopulations and thereby manipulate the type of immune response genera ....Dendritic cells are important sentinel cells of the immune system that orchestrate our immune responses against invading pathogens. There are different types of dendritic cells and they perform different jobs. We have a series of antibodies that can recognise markers on the surface of different dendritic cells populations. We can use these antibodies as homing devices to deliver foreign material to individual dendritic cell subpopulations and thereby manipulate the type of immune response generated. Effectively, we aim to tailor immune responses to fight a particular bacteria, virus, parasite, or even cancer cells. The current proposal will extend the number of antibodies we test for their ability to generate tailored immunity. We will examine a number of new molecules for their ability to shuttle foreign material to dendritic cells and their ability to stimulate immune responses. Next, we will test these homing devices as vaccines and their ability to prevent or treat cancer. Our aim is to develop a robust, highly efficient, generic, vaccination approach for cancer immunotherapy.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.
Deriving Actionable Strategies To Enhance Cancer Immunotherapy Response
Funder
National Health and Medical Research Council
Funding Amount
$447,193.00
Summary
Cancer immunotherapy is an increasingly common treatment used to treat several types of advanced cancers. Whilst it can be dramatically effective in a minority of patients, many patients do not respond to the treatment and our ability to predict who will not benefit is limited. This project aims to study distinct aspects of tumour immunology in patients receiving immunotherapy treatments in order to identify better predictors and more widely-effective immunotherapy treatment strategies.
Repurposing Thalidomide Derivatives To Augment Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$1,154,196.00
Summary
Immunotherapies are a revolutionary approach for cancer treatment, but most people with cancer do not respond to therapy. We have identified a new set of molecular switches that shutdown immune function and limit responsiveness to existing immunotherapies. Importantly, we have found a class of approved drugs that can block these immune 'off switches'. This proposal will test if these drugs could be repurposed as a novel treatment to amplify the efficacy of existing immunotherapies.
Aldehyde-modified Antigens For The Immunotherapy Of Adenocarcinomas
Funder
National Health and Medical Research Council
Funding Amount
$284,250.00
Summary
The incidence of breast cancer in women is 1 in 8 and the frequency of other cancers are rising. Even with conventional approaches such as surgery, cytotoxic therapy, radiotherapy and combination therapy only a few cancers are treatable. The development of a cancer vaccine will greatly benefit humanity similar to childhood and adult vaccinations for preventing infectious disease. In this proposal we intend to chemically modify a synthetic protein called mucin 1 (MUC1) which is exprssed on cells ....The incidence of breast cancer in women is 1 in 8 and the frequency of other cancers are rising. Even with conventional approaches such as surgery, cytotoxic therapy, radiotherapy and combination therapy only a few cancers are treatable. The development of a cancer vaccine will greatly benefit humanity similar to childhood and adult vaccinations for preventing infectious disease. In this proposal we intend to chemically modify a synthetic protein called mucin 1 (MUC1) which is exprssed on cells in breast cancer to make it more immunogenic - that is make it look more like a foreign protein so that the immune cells can make antibodies or killer cells that recognise it. These activated cells can now migrate to the tumour sites and kill the invading tumour. In order to do this we are going to introduce mannose, a particular sugar that can bind to important white blood cells and an aldehyde group that can activate immune cells. We will test the effectiveness of the modified proteins in mice to see if they can generate an good immune. If this is satisfactory then we will see if mice are vaccinated with these modified proteins can reject implanted mouse or human tumours. If these experiments are successful further work can be done with human cells and later clinical trials. Any methods developed here will be applicable to other cancers and also infectious diseases.Read moreRead less
Therapeutic Vaccine Against Non-Hodgkin's Lymphoma Targeting The Immune Adjuvant Properties Of Natural Killer T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$451,606.00
Summary
Patients with lymphoma cancers initially respond well to treatment, but later relapse with disease. The immune system can be effective at controlling cancer. A potential treatment option is to boost the natural immune response against cancer. This study investigates a vaccine that activates a certain immune cell, NKT cells, to fight lymphomas by delivering an NKT cell-activating molecule. Outcomes will allow assessment of combining an NKT-based vaccine with established treatments for lymphoma.
Understanding The Mechanism And Significance Of CXCL16-mediated Protection Of Tumour Cells From CTL-induced Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$524,520.00
Summary
This research will begin to determine the significance of changes in the amount of a recently-discovered protein on the surface of tumour cells. We have shown that an increase in expression of this protein protects tumour cells from destruction by our immune system's killer T cells. The outcome of this research could lead to a better understanding of how the immune system recognises and kills tumour cells, and ultimately, alternate vaccine strategies for tumours.
Identification Of CIS As A Potent Checkpoint In NK Cell-mediated Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$959,596.00
Summary
Cancer must evade detection by the immune system in order to develop. Natural Killer (NK) cells can detect and kill cancer cells. We have discovered a potent "checkpoint" in the NK cell activation pathway that desensitises NK cells to growth factors and switches off their activation and killer function. When this checkpoint is inhibited, NK cells are super activated and can prevent most types of cancer metastasis in mice. Targeting this checkpoint in humans could revolutionise cancer therapy.
Dynamic In Vivo Imaging Of Molecular And Cellular Events Shaping The Immune Response In Mouse Models And Human Diseases
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
We plan to develop the instruments and associated technologies required to directly visualise biological processes as the occur in real-time deep inside living organisms. Thus we will use two-photon microscopy to provide deep tissue imaging of immune cell interactions in mouse models and confocal endomicroscopy to provide molecular imaging of cancer biomarkers in patients with colorectal cancer.