Antibody-mediated Dendritic Cell Depletion To Attenuate GVHD
Funder
National Health and Medical Research Council
Funding Amount
$434,510.00
Summary
Not all patients with leukemia will be cured by chemotherapy. Stem cell transplantation improves their chances of survival. Stem cell transplantation requires intensive chemotherapy and radiotherapy to eradicate the underlying disease and infusion of healthy stem cells to provide an anti-leukemic effect and normal blood cells. Recovery from transplantation is not straightforward. Recovery can be hampered by the immunological reaction of the donor cells against the patient (Graft versus Host Dise ....Not all patients with leukemia will be cured by chemotherapy. Stem cell transplantation improves their chances of survival. Stem cell transplantation requires intensive chemotherapy and radiotherapy to eradicate the underlying disease and infusion of healthy stem cells to provide an anti-leukemic effect and normal blood cells. Recovery from transplantation is not straightforward. Recovery can be hampered by the immunological reaction of the donor cells against the patient (Graft versus Host Disease [GVHD]), despite immunosuppression. GVHD produces serious damage to the internal organs and lining of the mouth and gut. Recovery can also be circumvented by leukemic relapse. GVHD is associated with an increased risk of death and dying after transplantation. To date therapy for GVHD has relied on eliminating the T cells that cause the disease. However for T cells to cause damage they must first be primed with antigen presented on activated dendritic cells. The intensive conditioning therapy required to eradicate the underlying disease before transplantation also activates dendritic cells. Our project seeks to investigate the effects of lethal and non-lethal conditioning on dendritic cells with the aim of validating the use of antibodies designed to deplete activated dendritic cells as therapy for graft versus host disease.Read moreRead less
The transplantation of healthy stem cells from a donor into a recipient with blood cancer (stem cell transplantation) is the most effective curative therapy for the majority of patients. Unfortunately this process results in unwanted, often fatal, side effects including infection, a rejection process known as graft-versus-host disease and in some patients, the leukaemia still recurs. This research will refine new treatments focused on overcoming these limitations and improving transplant outcome
Immunological Therapies For Cancer And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$4,928,323.00
Summary
The programme team comprises a group of leading scientists with a history of successful investigation into the mechanisms and treatment of diseases in which the immune system plays a role in their development. These include cancers of the cervix and blood system, and autoimmune diseases such as rheumatoid arthritis and type 1 diabetes. Working together, the team have made discoveries that have led to testing and clinical development of new treatments for these diseases. In this programme, the te ....The programme team comprises a group of leading scientists with a history of successful investigation into the mechanisms and treatment of diseases in which the immune system plays a role in their development. These include cancers of the cervix and blood system, and autoimmune diseases such as rheumatoid arthritis and type 1 diabetes. Working together, the team have made discoveries that have led to testing and clinical development of new treatments for these diseases. In this programme, the team aims to discover mechanisms regulating the immune response, and to exploit this knowledge to define new ways of switching on or off, specific immune responses. We will particularly seek to develop novel vaccines for chronic infections and autoimmune diseases, and to improve the safety of bone marrow transplantation.Read moreRead less
Modulation Of Cytokine Responses To Improve Transplant Outcome.
Funder
National Health and Medical Research Council
Funding Amount
$26,186.00
Summary
Bone marrow transplantation remains a mainstay of curative therapy for haematological malignancies. This curative effect is mediated by the transplanted donor immune system which rejects the recipient malignancy. However, the procedure is limited by its serious side effect, known as graft-versus-host disease. This application seeks to better understand these two processes at both an immunological and clinical level with the aim of separating the two so that more patients may be cured of leukaemi ....Bone marrow transplantation remains a mainstay of curative therapy for haematological malignancies. This curative effect is mediated by the transplanted donor immune system which rejects the recipient malignancy. However, the procedure is limited by its serious side effect, known as graft-versus-host disease. This application seeks to better understand these two processes at both an immunological and clinical level with the aim of separating the two so that more patients may be cured of leukaemia.Read moreRead less
The Role Of Dendritic Cells In Graft-versus-host Disease After Allogeneic Stem Cell Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$317,633.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. Research to date by Dr Hill and colleages has provided substantial detail on how and why this process occurs. This information has led to a number of advances in the field which are already improving patient survival after BMT. This includes a new type of bone marrow transplantation that uses a naturally ocurring growth factor (called a cytokine) to allow the collection of immature bone marrow cells from the blood of transplant donors. The transplantation of these cells rather than bone marrow appears to reduce the chance of dying during BMT and also improves the cure rates from the underlying leukemia. In addition, Dr Hill has developed a novel method for preventing GVHD using different types of naturally ocurring growth factors called cytokine shields that help protect patient tissue from attack by the immune system. It has recently become clear that the immune system is directed by a subtype of white cells called dendritic cells and Professor Hart at the Mater Medical Research Institute has been a pioneer in this field. As initiators of the immune system it is likely that dendritic cells play a pivotal role in GVHD and Dr Hill and Prof Hart at the Mater Medical Research Institute will study DC within the context of Dr Hills newly developed therapies with the aim of further understanding the processes of GVHD. This work will allow manipulation of these cells during BMT in order to improve patient survival.Read moreRead less