Cancers have thousands of mutations, so they should look a bit like a viral infection. If so, why doesn’t the immune system just destroy them outright, like they would a virus? We think the mutated proteins cause a ‘brake’ to be put on the anti-cancer immune response, and also that cancers subvert the anti-cancer attack by remaining hidden in the target zone. Unblocking these “brakes” might lead to new treatments.
Cancer Chemo-immunotherapy: Exploiting The Immunogenic Momentum Of Cytotoxic Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$917,490.00
Summary
We recently found that chemotherapy has beneficial effects on the immune response against cancer rather than ill effects. Here we want to exploit this positive effect by combining different chemotherapeutics with immune-stimulating treatments in laboratory models. These studies will result in a better understanding of how chemotherapy influences the immune system, and may also result in new combinations that improve the effectiveness of cancer therapy.
Adoptive Cell Transfer Incorporating Vaccination (ACTIV) Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
We have made a breakthrough in a new treatment for cancer that can destroy large tumours in mice. The treatment involves a transfusion of white blood cells and an injection of a vaccine. In this project, we will seek to understand how the treatment works, and apply it to human white blood cells in preparation for a clinical trial in cancer patients.
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
Significance Of Soluble PD-L1 In Melanoma Patients
Funder
National Health and Medical Research Council
Funding Amount
$561,236.00
Summary
A class of new immunotherapy drugs called “antibodies of immune checkpoints” can lead to long-lasting melanoma regression, but they are only beneficial to a subset of patients. This project will potentially identify the increased expression of a protein called PD-L1 in the blood as a biomarker predictive of responses of melanoma patients to these new drugs. The results will be instructive for selection of patients for the treatment.
A 2:1 Randomised Phase II Study Of NivolUmab And Temozolomide Vs Temozolomide In Methylated Newly Diagnosed Elderly Glioblastoma (NUTMEG)
Funder
National Health and Medical Research Council
Funding Amount
$1,608,845.00
Summary
Radiotherapy and Temozolomide (TMZ) chemotherapy treatment for the brain tumour glioblastoma (GBM) is not as effective in elderly patients. If their tumour has a genetic marker called "methylated MGMT", TMZ does work relatively better and is often given alone. Elderly GBM patients with this marker will be randomly selected in this trial to have TMZ alone or TMZ + Nivolumab - a drug that assists the immune system to attack cancer.
The Role Of CD73 In Cancer: Validating A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
We here propose to investigate the role of a specific immune-suppressive molecule called CD73 in cancer. We will test the therapeutic activity of blocking CD73 with a monoclonal antibody for cancer treatment, either used alone or in combination with immune-activating agents and chemotherapy.
Genetic Engineering Of Tumor-infiltrating Monocytes To Inhibit Primary And Metastatic Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$792,470.00
Summary
The immunosuppressive environment within a tumour is the major impediment to the successful application of cancer immunotherapy. To address this, we developed a cell- and gene-based strategy for targeted delivery of a potent immune-stimulatory molecule, IFN-?, which activates the immune response at the site of the tumour. We now propose to combine this strategy with promising cancer immunotherapies for the treatment of advanced breast cancer and breast cancer metastasis.
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.
Immunotherapy is a new approach to treat cancer, and works by promoting the immune system to attack cancer. Immunotherapies, such as checkpoint blockade and adoptive T cell therapy, are proving to be very successful in certain human cancers. However, combining immunotherapy with drugs that cause cancer cell death may be more effective. This project will investigate the potential of combining immunotherapy with a novel anti-cancer drug, in order to develop more effective treatments for cancer.