Characterization And Targeting Of Precursor Exhausted T Cells (TPEX) For The Treatment Of Chronic Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,009.00
Summary
The recent discovery of precursor exhausted CD8 T cells (TPEX) has not only allowed us to conceptualize our understanding of how chronic T cell responses are maintained over long periods of time, but also resulted in a new understanding of the mechanisms underpinning checkpoint inhibition. I will undertake critical characterization of these TPEX in chronic viral infections with the goal to reveal phenotypic and functional properties, which will serve as potential novel targets for immunotherapy.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
Tumor Targeted T Cells To Enhance Anti-tumor Efficacy And Dictate Umbilical Cord Blood (UCB) Engraftment In The Setting Of Double UCB Transplant.
Funder
National Health and Medical Research Council
Funding Amount
$376,002.00
Summary
Currently, despite cord blood transplantation, most leukemia patients will ultimately die of disease relapse. Therefore, my proposal is focused on improving the effectiveness of cord blood transplantation by further infusion of gene modified umbilical cord derived immune blood cells designed to specifically target and lyse residual leukemia tumor cells. This novel approach this will decrease disease relapse and lead to better patient survival following cord blood transplant therapy.
Development Of Novel Immunotherapeutic Approaches For The Treatment Of Epstein-Barr Virus-associated Malignancies.
Funder
National Health and Medical Research Council
Funding Amount
$378,940.00
Summary
Epstein-Barr virus (EBV) is attributed to cause 200,000 cancer cases annually. Malignancies associated with EBV include nasopharyngeal carcinoma and Hodgkins lymphoma. These malignancies have been treated, with limited success, by “adoptive immunotherapy” in which the patients T cells are expanded in the laboratory by stimulation with this virus, and infused back into the patient. This project aims to assess three novel approaches to enhance this form of treatment for therapeutic consideration.
Overcoming Resistance To Cancer Immunotherapy By Targeting MET-signaling In Neutrophils
Funder
National Health and Medical Research Council
Funding Amount
$447,375.00
Summary
Cancer is a leading cause of death in Australia. The human immune system is able to attack cancer cells. However, cancer cell can escape the destruction by cytotoxic cells. The development of novel immunotherapies has revolutionized cancer therapy, but only a subgroup of patients is responding. This research project aims to identify novel combinatorial therapies blocking immune suppressive neutrophils to improve anti-cancer immunity and survival of cancer patients.
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
The human immune system comprises many different types of cells that can detect foreign molecules. My research will lead the way to understanding some of the most abundant, yet least well understood, cells within this system, collectively known as 'unconventional T cells'. This knowledge is essential to optimally and efficiently manipulate the immune system in health and disease.
Molecular Regulation Of Tim3 Signalling In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Chronic inflammatory diseases like multiple sclerosis and cancer can be rectified via interventions of T cell checkpoint pathway. Tim3 is a T cell checkpoint molecule that is gaining extreme interest in these diseases. Here, we aim to identify molecular mechanism(s) to suppress or enhance Tim3 signalling in effector T cell, potentially leading to the development of therapeutic intervention to treat autoimmune disorders and cancers.
My research is aiming to study how the immune system controls viral infections in transplant patients and use this information to bolster their immunity in a test tube, providing protection against a virus the patient is unable to fight after their transplant. We are also trying to develop new strategies to use patient's own blood cells which will be grown in the laboratory and returned to the patient, resulting in a full recovery.
Australia has one of the highest asthma rates in the world. In this project we will study how natural regulatory T cells suppress asthma in a mouse model. We will determine where and when interactions between regulatory T cells and allergic T cells occur, and define the mechanisms used by regulatory cells to mediate their suppressive effects. Our findings will aid in understanding why asthma develops and how it may be controlled by the immune system itself.