Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.
Development Of Cancer Immunotherapy Using Gene-engineered T Cells In A Self-antigen Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$428,602.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells.
The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. In this project, we make use of special microscopes to examine the glomerulus during an inflammatory response, with the aim of understanding the actions of leukocytes present in glomeruli and how they cause inflammation and damage the glomerulus.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
The Role Of Non-classical MHC Class I Molecules In Adaptive Immunity
Funder
National Health and Medical Research Council
Funding Amount
$443,834.00
Summary
Specialised proteins called MHC class Ia molecules (MHC-Ia) stimulate killer T cells to lyse virus infected cells. In contrast, the function of the closely related MHC-Ib is uncertain. Recent findings have demonstrated that MHC-Ib can also be recognised by T cells and this interaction is important in the control of viral infections. However, despite the similarity to MHC-Ia, it is unclear how this interaction occurs. This project aims to investigate how killer T cells recognise MHC-Ib molecules.
Generation Of Protective Immunity Against Severe Influenza Disease In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$1,630,970.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population, especially when a new virus emerges. There is an urgent need for a vaccine that protects against all influenza strains. T cells recognising conserved viral regions elicit such protection. As T cells are restricted by proteins called HLAs, which vary across ethnicities, we will define T cell regions for HLAs prominent in Indigenous Australians and define how to generate protective immunity against influenza.