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
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
Over 10,000 persons per year in Australia are diagnosed with a blood cancer, accounting for 11% of cancer deaths. Stem cell transplantation remains curative therapy for these diseases but is limited by cancer relapse and an immune-mediated process known as graft-versus-host disease (GVHD) which account for death of up to 50% of patients. This CRE will integrate centres from Australia and the USA to coordinate new treatments in transplant and cell therapy to improve blood cancer outcomes.
The Structural Basis For Recognition Of HLA-E By Both Innate And Adaptive Immune Systems.
Funder
National Health and Medical Research Council
Funding Amount
$206,255.00
Summary
Biochemistry and structural biology can be used to understand and visualize the three dimesional shape of molecules and the way they interact with other molecules. We will use these approaches to understand how various cells of the immune system recognise the protein HLA-E. This protein is normally present on the surface of healthy cells while it frequently retained inside both tumours and cells infected with viruses. This acts a signal for the immune system to kill these cells. However to avoid ....Biochemistry and structural biology can be used to understand and visualize the three dimesional shape of molecules and the way they interact with other molecules. We will use these approaches to understand how various cells of the immune system recognise the protein HLA-E. This protein is normally present on the surface of healthy cells while it frequently retained inside both tumours and cells infected with viruses. This acts a signal for the immune system to kill these cells. However to avoid being recognized by the immune system some viruses have developed ways to maintain HLA-E expression. This grant will attempt to understand exactly how the immune sytem recognizes HLA-E and how it discriminates between HLA-Eexpressed by healthy cells compared with HLA-E expressed by a virus-infected cell.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.
Does Galalpha(1,3)Gal Still Play A Role In Xenograft Destruction After The Production Of Gal Knockout Pigs?
Funder
National Health and Medical Research Council
Funding Amount
$706,062.00
Summary
Advances in surgical and immunosuppressive techniques has led to organ transplantation as the method of choice for the treatment of many diseases. However, the number of suitable donors is dwindling, due to many factors, but largely as a result of the reduction in deaths from car accidents. Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors. The pig is the most suit ....Advances in surgical and immunosuppressive techniques has led to organ transplantation as the method of choice for the treatment of many diseases. However, the number of suitable donors is dwindling, due to many factors, but largely as a result of the reduction in deaths from car accidents. Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors. The pig is the most suitable for a variety of reasons. However, the problem is that all humans contain natural antibodies to the pig which would lead to rejection within a few minutes as the antibodies bind to the transplant and reverse its rapid destruction (so called hyperacute rejection). Recent studies from our laboratory have indicated that most, if not all, of the antibodies react with the sugar - galactose present on many molecules on the surface of transplanted pig tissues. Our studies have indicated very large amounts of this material present in pig blood vessels - guaranteeing the early rejection of transplanted organs such as kidney, heart and liver. The production of knockout pigs which do not express the galactose sugar is an important pre-requisite for successful xenotransplantation. Recently knockout pigs which lack an enzyme that makes this sugar have been produced, but not all the sugar was destroyed. We have recently described a second novel enzyme that also makes this sugar. We will examine a role of this enzyme in xenotransplantation. These studies will be the prelude to the production of pigs which could be used for human transplantation.Read moreRead less
Deciphering Mechanisms Of Liver Allograft Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$520,964.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Liver transplants are more readily accepted than other organ grafts in the absence of immunosuppressive drugs but little is known about the mechanisms that prevent an effective response. This proposal aims to unravel these mechanisms. This project will have important implications for transplantation studies.
Dendritic Cells In Graft-versus-Host Disease Following Bone Marrow Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$180,859.00
Summary
Bone marrow transplantation (BMT) is the only available curative therapy for many blood cancers such as leukaemia. Graft-versus-host disease (GVHD) occurs after BMT and is a major cause of transplant-related death. GVHD occurs when transplanted donor cells “attack” recipient tissues causing widespread damage. Gaining a more comprehensive understanding of this disease process is critically important for the design of new therapies and improvement of outcomes for transplant recipients.
The Role Of Alloantigen Presentation In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which d ....Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.Read moreRead less
Failure Of Donor Antigen Presentation Promotes IL-17 Dependant Chronic GVHD
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which d ....Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.Read moreRead less