An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.
GENETIC MANIPULATION OF TUMOURS TO INDUCE IMMUNE REJECTION
Funder
National Health and Medical Research Council
Funding Amount
$396,342.00
Summary
The ability to be able to modify tumour growth and bring about tumour rejection by activating the host immune system is a prime objective in many laboratories throughout the world. Our aim is to take advantage of the considerable advances in molecular technology of recent years to develop effective approaches to the modification of tumour cells so that their growth can be inhibited in vivo. The project has three main aims: (i) to identify combinations of genes which, when administered to or expr ....The ability to be able to modify tumour growth and bring about tumour rejection by activating the host immune system is a prime objective in many laboratories throughout the world. Our aim is to take advantage of the considerable advances in molecular technology of recent years to develop effective approaches to the modification of tumour cells so that their growth can be inhibited in vivo. The project has three main aims: (i) to identify combinations of genes which, when administered to or expressed in tumour cells will induce protective immune responses against the tumour (ii) to investigate the effectiveness of combination approaches to gene therapy whereby genetic manipulations which cause destruction of tumour cells, or inhibition of blood vessel growth in tumours can be combined with administration of immunologically relevant genes to enhance tumour destruction (iii) to identify molecules which can act as target tumour antigens for the immune response or which are involved in promoting tumour survival so that these genes may be manipulated to enhance the development of anti-tumour immunity. The model we will use to investigate these issues will be malignant mesothelioma (MM). This tumour type is currently untreatable and is resistant to all available forms of therapy. Achievement of the aims described above would lead to the capacity for early treatment of MM. The identification of suitable target antigens has the potential to lead to vaccination protocols for therapy or as a preventative measure. Furthermore, the principles defined in this project will be applicable to the treatment of a variety of other solid tumours which are currently resistant to conventional therapy.Read moreRead less
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
Utilization Of Gene-engineered T Cells For Enhancing Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$761,656.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells, whilst minimizing toxicity to normal tissue.
New Strategies For Enhancing Chimeric Antigen Receptor (CAR) T Cell Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$849,540.00
Summary
The role of the immune system in cancer is now recognised as highly important, highlighted by the success of immunotherapy in patients. Yet many patients fail to respond to this form of treatment due to low frequency of lymphocytes present at the tumor site. A new form of immunotherapy involving transfer of gene-modified lymphocytes is a potential way to overcome this problem. This project will explore new strategies to enhance the utility of this approach against blood and solid cancers.
Investigating The Anti-tumour Efficacy And On Target Toxicity Of Gene-modified T Cell Therapy In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. Although these cells can induce cancer regression when given back to the patient, these cells can often cause associated pathology. In this study we propose to fully investigate the limits of this type of therapy for mediating anti-tumour responses and potential toxicity in mouse models that closely recapitulate the human setting. These studies will lead to a more effective therapy for patients.
The Use Of Gene-Silencing Nanodrugs To Inhibit Lung Cancer Growth
Funder
National Health and Medical Research Council
Funding Amount
$452,950.00
Summary
Lung cancer accounts for the most cancer deaths worldwide. This research proposal will use state-of-the-art nanomedicines designed to penetrate lung tumours and suppress a gene which drives cancer growth and resistance to chemotherapy drugs. Our results could underpin new approaches that revolutionise more effective and less toxic treatments for a highly lethal malignancy.
My goal is to boost the immune system against cancer to develop new therapies. I aim to do this by genetically engineering the immune system and using drugs to help strengthen white blood cells of the immune system. Tumors can actively fight immunity by producing suppressive molecules. I am seeking to identify and understand these molecules in order to block them and help the immune system fight cancer. Using this knowledge, I aim to start new clinical trials for cancer.
Towards Effective Immunotherapy Of Cancer Using Genetically Enhanced Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Immunotherapy is a potentially powerful and specific form of cancer therapy that may be more effective and have fewer side effects than current forms of therapy including chemotherapy and radiotherapy. Already dramatic responses have been observed in a proportion of patients receiving immunotherapy for some malignancies but these responses are all too infrequent. T cells constitute an important part of the immune system but they often fail to recognize cancer and do not respond strongly enough a ....Immunotherapy is a potentially powerful and specific form of cancer therapy that may be more effective and have fewer side effects than current forms of therapy including chemotherapy and radiotherapy. Already dramatic responses have been observed in a proportion of patients receiving immunotherapy for some malignancies but these responses are all too infrequent. T cells constitute an important part of the immune system but they often fail to recognize cancer and do not respond strongly enough against tumours. This project investigates the feasibility of endowing patients' T cells with the abilities to recognize cancer and respond vigorously against it by genetically modifying the T cells. In this study, T cells are removed from mice that have cancer and a gene encoding an anti-cancer molecule inserted into the T cells. The T cells are activated, grown to large numbers and given back to tumour-bearing mice followed by booster vaccinations. The strategy used is novel and the proposed studies, together with preliminary data, represent the first investigations of their type in the world. Information derived from these studies will extend our understanding of tumour immunology and provide an appreciation of the importance of various parameters in achieving anti-tumour responses. Improved anti-tumour responses achieved through investigations in these proof-of-principle pre-clinical models could lead to more effective immunotherapeutic regimens in patients.Read moreRead less
An In-vivo Model Of Acquired Chemoresistance In Small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$363,827.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how a very aggressive form of lung cancer becomes resistant to chemotherapy. To do this, we use a new mouse model of lung cancer in which we can study how human lung cancer cells develop resistance to chemotherapy in vivo. Understanding these pathways will help us to better treat lung cancer with chemotherapy.