Inducible Caspase 9 Suicide Gene To Improve The Safety Of Donor T Cell Addback After Haploidentical Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$566,232.00
Summary
In bone marrow transplantation, donor immune cells are important for fighting cancer cells and infections but can also attack healthy tissues, causing graft-versus-host disease (GVHD). We will use gene technology to insert a safety switch called inducible capase 9 (iCasp9) into the donor immune cells which will make them susceptible to an otherwise non-toxic chemical. This will make it safer to boost the recipients’ immunity because these cells can be rapidly eliminated if GVHD occurs.
A Phase I Study Of Autologous CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Relapsed And Refractory B-cell Leukaemia And Lymphoma (The Auto-CAR19 Trial).
Funder
National Health and Medical Research Council
Funding Amount
$584,666.00
Summary
Most people with leukaemia and lymphoma who relapse early after chemotherapy die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but the cost of the viral vectors used to make these cells is prohibitively expensive. We will make leukaemia and lymphoma specific immune cells from patients using an inexpensive non-viral system, then administer the immune cells to patients to assess their safety and efficacy.
A Phase I Study Of PiggyBac CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Persistent And Relapsed B-cell Leukaemia And Lymphoma Post Allogeneic Stem Cell Transplantation (The CARTELL Study).
Funder
National Health and Medical Research Council
Funding Amount
$357,590.00
Summary
Most people with relapsed leukaemia and lymphoma after bone marrow transplant die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but there is little experience in bone marrow transplant patients. We will make leukaemia and lymphoma specific immune cells from normal bone marrow transplant donors, then administer the immune cells to transplant patients to assess their safety and effectiveness.
Harnessing RNA Interference In Gene Therapy Vectors For ?-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$719,188.00
Summary
There is an urgent need to develop safe and effective treatments for ?-thalassaemia. We anticipate that ?-globin-specific RNAi sequences will synergise with ?-globin transgene expression to achieve balanced ?-/?-globin ratio in a clinical setting. Given that one of the major issues with current gene therapy vectors is achieving high levels of expression, we believe this will be a more effective gene therapy strategy than ?-globin transgene expression alone.
Zbtb11 is a druggable protein that is mis-expressed in blood cancers - second biggest cause of cancer death in Australia - and liver cancer, third leading cause of death from cancer worldwide. We have found that it interacts with 2 other proteins with potential roles in these diseases. Our studies examine the nature of these Zbtb11-partner interactions and their particular consequences for blood disorders. Zbtb11 contributions to disease development will be a target for novel disease therapy.
Redirecting T-cells For Immunotherapy Of Leukaemia And Lymphoma By The Expression Of A CD19-specific Chimeric Antigen Receptor Using The PiggyBac Transposon Gene Modification System
Funder
National Health and Medical Research Council
Funding Amount
$374,876.00
Summary
Most lymphomas respond to therapy but then relapse. Immune cells can attack and kill virus related lymphomas. However, most lymphomas are NOT virus related. We will create immune cells targeting these virus negative lymphomas by inserting artificial receptors into the immune cells. These receptors attach to the lymphoma and activate the immune cells. The immune cells will home to the lymphoma, kill lymphoma cells and persist in the body for many years, preventing lymphoma relapse.
Role Of Zeb2/Sip1 In Leukaemic Stem Cell Formation And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$655,174.00
Summary
T-cell acute lymphoblastic leukaemia (T-ALL) results from the abnormal development of T cells that are an important cell type in the body's immune system. Although the prognosis for T-ALL has improved remarkably over the last decade, for one out of five T-ALL cases the underlying genetic defects remain unresolved and are refractory to current therapies. This project aims to use both novel mouse models and human patient cell lines to better understand this disease and discover novel targets for f ....T-cell acute lymphoblastic leukaemia (T-ALL) results from the abnormal development of T cells that are an important cell type in the body's immune system. Although the prognosis for T-ALL has improved remarkably over the last decade, for one out of five T-ALL cases the underlying genetic defects remain unresolved and are refractory to current therapies. This project aims to use both novel mouse models and human patient cell lines to better understand this disease and discover novel targets for fighting this disease.Read moreRead less
A Novel Genetic Element Controlling Adult Hemoglobin Production
Funder
National Health and Medical Research Council
Funding Amount
$493,907.00
Summary
Disorders of the blood protein hemoglobin are the commonest genetic diseases worldwide, and include thalassemia and sickle cell disease. In this proposal we study two novel mouse lines that exhibit thalassemia, but lack any of the known genetic mutations that cause this disease. These mice afford us the opportunity to make unique observations into how hemoglobin is produced, and thereby provide a platform for new therapeutic approaches in these devastating diseases of the blood.
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
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