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.
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.
Feature Learning for High-dimensional Functional Time Series. This project aims to develop new methods and theories for common features on high-dimensional functional time series observed in empirical applications. The significance includes addressing a key gap in adaptive and efficient feature learning, improving forecasting accuracy and understanding forecasting-driven factors comprehensively for empirical data. Expected outcomes involve advances in big data theory and easy-to-implement algori ....Feature Learning for High-dimensional Functional Time Series. This project aims to develop new methods and theories for common features on high-dimensional functional time series observed in empirical applications. The significance includes addressing a key gap in adaptive and efficient feature learning, improving forecasting accuracy and understanding forecasting-driven factors comprehensively for empirical data. Expected outcomes involve advances in big data theory and easy-to-implement algorithms for applied researchers. This project benefits not only advanced manufacturing by finding optimal stopping time for wood panel compression, but also superior forecasting for mortality in demography, climate data in environmental science, asset returns in finance, and electricity consumption in economics. Read moreRead less
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.
Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interaction ....Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interactions and be used as lead compounds for treatments for disease.Read moreRead less
The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increa ....The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increasing the profitability and ensuring the sustainability of both the dairy and meat industries. Better understanding of the mechanisms controlling mammary epithelial cell differentiation should enable augmentation of lactation such as increasing milk protein content, using marker assisted selection (of targets such as Runx2) in cattle.Read moreRead less
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.Read moreRead less
The effect of nitrogen monoxide on intracellular iron metabolism. We discovered that the crucial signalling molecule nitrogen monoxide (NO) mediates iron (Fe) and glutathione (GSH) release by the transporter MRP1 probably as an NO-Fe-GSH complex [DR(2006) PNAS USA 103:7670-5]. During our current ARC grant we have markedly extended these findings by showing that another molecule, GST Pi and MRP1 form part of a coordinated system that stores and transports NO as complexes of Fe and GSH, markedly e ....The effect of nitrogen monoxide on intracellular iron metabolism. We discovered that the crucial signalling molecule nitrogen monoxide (NO) mediates iron (Fe) and glutathione (GSH) release by the transporter MRP1 probably as an NO-Fe-GSH complex [DR(2006) PNAS USA 103:7670-5]. During our current ARC grant we have markedly extended these findings by showing that another molecule, GST Pi and MRP1 form part of a coordinated system that stores and transports NO as complexes of Fe and GSH, markedly extending NO half-life from milliseconds to hours. This has broad implications for understanding NO activity in many processes which have major vital health implications, including tumour cell killing by macrophages and blood pressure control.Read moreRead less
The Effect of Nitrogen Monoxide on Intracellular Iron Metabolism. For the first time, we discovered that nitric oxide (NO) is actively transported from cells by a protein that is known to also transport glutathione (GSH). This is important, as NO was thought to passively diffuse from cells. Active transport overcomes the problems of diffusion which is inefficient and non-targeted. Moreover, NO is released as a complex with iron and GSH which markedly increases its half-life. These findings have ....The Effect of Nitrogen Monoxide on Intracellular Iron Metabolism. For the first time, we discovered that nitric oxide (NO) is actively transported from cells by a protein that is known to also transport glutathione (GSH). This is important, as NO was thought to passively diffuse from cells. Active transport overcomes the problems of diffusion which is inefficient and non-targeted. Moreover, NO is released as a complex with iron and GSH which markedly increases its half-life. These findings have broad implications for understanding the activity of NO in many processes which have major health implications, including tumour cell killing by macrophages, blood pressure etc.Read moreRead less