Deciphering IFN Type III, TGF?, IL-10 And Adenosine Pathways In Natural Killer Cells: Enhancing The Innate Anti-metastatic Response Against Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
This project will determine whether one or more factors produced in tumours (eg. cell hormones and metabolites) inhibits NK cells from controlling breast cancer spread using the best available mouse tumour models. We will use genetics to specifically delete response to these factors by NK cells. It is a completely novel approach and this information will allow for the more rational design of cancer treatments following surgery and local radiotherapy and/or chemotherapy.
Control Of Haematological Cancers By Natural Killer Cells
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Haematological cancers affect the blood and lymphoid organs and are generally lethal. Therapies targeting the anti-tumour capacities of the immune system have shown promising results in cancer patients. Natural Killer (NK) cells are key players of anti-tumour immune responses. This project will provide a better understanding of NK cell-mediated control of haematological malignancies that will be directly applied to the design of new curative therapies for blood cancer patients.
The Differential Contribution Of Programmed Death-1 Ligands To Malarial Immunity
Funder
National Health and Medical Research Council
Funding Amount
$327,784.00
Summary
This research aims to understand how the Malaria parasite, which causes one of the world’s deadliest diseases, evades immunity. It will provide a significant advance in our knowledge of immunity against malaria and impact on current strategies to develop an efficacious vaccine or treatment for malaria.
Modulation Of HIV-1 Latency In Primary CD4 T Cells By Chemokines And Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$380,167.00
Summary
Although treatment of HIV using antiretroviral drugs has dramatically improved outcome the presence of latent infection in long lived T cells has so far prevented cure of HIV infection. This study examines the roles of chemokines (proteins that control cell migration) and a special type of infection fighting cell, the dendritic cell, in generating latent infection in resting T cells. These studies could potentially identify new ways to treat and potentially cure HIV infection.
Cancer Immunotherapy Utilizing A Novel Receptor For Programmed Cell Death-1 Ligand 2
Funder
National Health and Medical Research Council
Funding Amount
$577,857.00
Summary
Immuno-modulators utilize the patient’s own immune system to eliminate or slow the growth of cancerous cells. We have identified a novel immuno-modulator which could be a significant player in immune-modulation therapy for the treatment of cancer. We will use the development grant to develop a product which has significant potential to be the next generation treatment for cancer.
Targeting Epigenetic Mechanisms Of Immune Evasion In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,425,280.00
Summary
Proteins called MHC class I and II on the surface of cancer cells act as sensors that allow the immune system to recognise cancer cells as abnormal and destroy them. However, cancer cells have developed ways to hide from the immune system by silencing MHC class I and II. This project aims to identify ways to overcome this silencing and restore MHC class I and II to the surface of the cancer cells, allowing them to be treated with therapies that activate immune cells to eradicate the tumour.
The Role Of MHC In Immune Evasion: Insights From A Contagious Cancer
Funder
National Health and Medical Research Council
Funding Amount
$260,677.00
Summary
An aggressive, contagious cancer, Devil Facial Tumour Disease (DFTD), has emerged in the Tasmanian devil population. We are using the devil tumour to study how cancer is recognized by the immune system and ways in which cancer can 'escape' from the immune system. This research will contribute to our understanding of human cancer and help save an iconic Australian species from extinction.
Exploiting Anti-capsid Humoral Immunity Induced In Infants Receiving Gene Therapy For Spinal Muscular Atrophy To Engineer The Next Generation Of Gene Transfer Vectors
Funder
National Health and Medical Research Council
Funding Amount
$1,105,993.00
Summary
After 25 years of incremental progress the possibility of treating genetic disease by gene therapy has become a therapeutic reality. This has been achieved by harnessing the gene transfer power of viruses made harmless by genetic engineering. A major limitation is that up to 50% of patients are currently excluded by pre-existing immunity to these powerful tools. Using 'evolution in a dish', we will engineer a new generation of these tools capable of bypassing pre-existing immunity by stealth.
Immunobiology Of Early Pregnancy - A Model Of Virus-induced Abortion
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft trans ....The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft transplantation. Infection with flaviviruses increases the concentrations of cell surface self and adhesion molecules in vertebrate cells, including the trophoblast cells of the placenta. As a result, these molecules can then be recognised by the maternal immune system and the embryo targeted for destruction. We hypothesise that the induction of these molecules by this and other viruses may break the immunological silence of the early embryo and reverse the local suppression of the maternal immune response. This would result in maternal immune rejection of the embryo and abortion. This initial sensitisation of the mother by the virus might be one of the reasons that some women suffer recurrent abortions. We will use a novel viral mouse model where we implant virus-infected embryos into receptive animals to enable us to dissect out the unusual requirements for induction of maternal anti-viral immunity during pregnancy. This model was developed in our laboratory to directly test our hypotheses. It does not cause systemic illness in the mother which itself can lead to non-specific abortion. This model therefore can for the first time elucidate the specific mechanisms associated with the delicate balance between eradicating virus and maintaining pregnancy. Results from this project will inform rational design of treatment of recurrent abortions in the community.Read moreRead less