IL-6 As The Key Inflammatory Mediator Controlling GVHD
Funder
National Health and Medical Research Council
Funding Amount
$592,049.00
Summary
Allogeneic haematopoietic stem cell transplantation (SCT) is a curative treatment for blood cancers. Graft-versus-host disease (GVHD) is a major limitation which occurs when the newly transplanted immune system mounts a rejection response against the recipient and is responsible for the death of up to 40% of transplant recipients. These studies will optimize a new approach to prevent GVHD focusing on a protein called interleukin-6. Ultimately, it is anticipated such approaches will improve the o ....Allogeneic haematopoietic stem cell transplantation (SCT) is a curative treatment for blood cancers. Graft-versus-host disease (GVHD) is a major limitation which occurs when the newly transplanted immune system mounts a rejection response against the recipient and is responsible for the death of up to 40% of transplant recipients. These studies will optimize a new approach to prevent GVHD focusing on a protein called interleukin-6. Ultimately, it is anticipated such approaches will improve the overall survival of patients with blood cancers.Read moreRead less
Novel Biocompatible Nickel-free Shape Memory Alloy Scaffolds For Biomedical Applications
Funder
National Health and Medical Research Council
Funding Amount
$530,789.00
Summary
The current project is aimed at the development of a new class of novel biocompatible nickel-free shape memory alloy (SMA) scaffolds for metallic implant applications. The new scaffolds possess the ability to exert a mechanical force on the surrounding bones, and stimulate new bone tissue ingrowth, due to their shape memory effect, superelasticity and bone-mimicking porous structure. The outcomes from this project will provide innovative implant materials.
Targetting Monocytes With Microparticles To Prevent Kidney Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$967,005.00
Summary
Whilst transplantation is lifesaving for many Australians with organ failure, it is a treatment rather than cure as recipients are dependent upon lifelong immunosuppression to prevent transplant rejection. Risks of death due to infection and cancer therefore remain high. We will test a new strategy in mice which modifies recipients of monocytes at the time of transplantation, to enable them to accept and tolerate the organ without ongoing need for expensive and dangerous immunosuppressive drugs.
Bioengineering Synthetic Elastin Conduits For Arterial Revascularisation
Funder
National Health and Medical Research Council
Funding Amount
$624,776.00
Summary
An arterial substitute with both physical and biological properties that mimic those of the human vasculature has long been the holy grail of vascular tissue engineering. We propose synthetic elastin can form the basis of a durable, clinically effective small diameter vascular graft and fill a significant unmet need for a biocompatible vascular substitute.
TOLERANCE OR REJECTION – THE ROLE OF INNATE IMMUNITY IN DETERMINNG THE FATE OF A KIDNEY ALLOGRAFT
Funder
National Health and Medical Research Council
Funding Amount
$506,413.00
Summary
Transplantation is the optimal management for people with organ failure. Tolerance, to retain transplant function without immunosuppression, remains the key goal but is seldom achieved. We propose to block Toll-like receptor signalling to achieve kidney transplant tolerance in mice. If successful, we would translate this into clinical trials in human, seeking to achieve organ transplantation without the risks of cancer, infection and premature death that are currently faced by organ recipients.
Conquering The Final Frontier In Lung Transplantation - Mesenchymal Stromal Cell Therapy For Chronic Lung Allograft Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$1,887,790.00
Summary
Lung transplantation remains the only treatment option for an increasing number of Australians with end-stage lung disease, however long-term outcomes are severely compromised by the almost universal development of chronic rejection. Mesenchymal stromal cells (MSCs) hold great promise in treating rejection, and in a world-first we have recently demonstrated that this approach is safe. In another world-first, this randomized, controlled study will determine whether MSC therapy is effective.
Activin A And Follistatin Are Potential Key Regulators Of Organ Transplant Dysfunction And Graft Survival.
Funder
National Health and Medical Research Council
Funding Amount
$535,579.00
Summary
The grant examines novel key regulators in organ transplantation. It examines molecules that are released during transplant surgery and on the return of blood flow to the organ which can cause inflammation and scarring. The release is increased by heparin, an anticoagulant used in organ preparation. Alternative anticoagulants and blockers of the regulators released will be tested to prevent the damage to the transplant, potentially improving both the short and long term graft survival and functi ....The grant examines novel key regulators in organ transplantation. It examines molecules that are released during transplant surgery and on the return of blood flow to the organ which can cause inflammation and scarring. The release is increased by heparin, an anticoagulant used in organ preparation. Alternative anticoagulants and blockers of the regulators released will be tested to prevent the damage to the transplant, potentially improving both the short and long term graft survival and function.Read moreRead less
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.
A Phase 1 Clinical Trial Of A Human Chimeric Anti-Activated DC Antibody To Prevent AGVHD In High Risk Allo HSCT.
Funder
National Health and Medical Research Council
Funding Amount
$670,736.00
Summary
Bone Marrow transplants provide life saving therapy for leukaemias, lymphomas and other life threatening blood disorders. One of the major life threatening complications is acute graft versus host disease (AGVHD) in which the doner immune system damages the patient's skin, liver and gut, amongst other tissues. Dendritic cells initiate and direct immune responses. We have shown that dendritic cells are central to the initiation of AGVHD and have shown that a marker called CMRF-44 is expressed on ....Bone Marrow transplants provide life saving therapy for leukaemias, lymphomas and other life threatening blood disorders. One of the major life threatening complications is acute graft versus host disease (AGVHD) in which the doner immune system damages the patient's skin, liver and gut, amongst other tissues. Dendritic cells initiate and direct immune responses. We have shown that dendritic cells are central to the initiation of AGVHD and have shown that a marker called CMRF-44 is expressed on activated dendritic cells before AGVHD emerges. We have developed potential new therapeutic antibodies that target activated dendritic cells and shown that they are effective in preclinical studies. This project will further validate these antibodies, then test their safety and their ability to prevent AGVHD in patients. The trial will also test whether they have the expected additional beneficial effect of preserving protective anti-viral and anti leukaemic immune responses.Read moreRead less
Cytokine Responses Within The GI Tract Dictate T Cell Fate And Transplant Outcome
Funder
National Health and Medical Research Council
Funding Amount
$1,479,579.00
Summary
Over 10,000 persons per year in Australia are diagnosed with a blood cancer, accounting for 10% of cancer deaths. Stem cell transplantation remains curative therapy for these diseases but is limited by a process known as graft-versus-host disease (GVHD), responsible for mortality in up to 50% of patients. This project will focus on immune responses within the colon as the critical event initiating lethal GVHD, defining new treatments that will be translated to improve transplant outcomes.