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.
THE ROLE OF TUMOUR-EGRESSING T CELLS IN ANTI-TUMOUR IMMUNE RESPONSES
Funder
National Health and Medical Research Council
Funding Amount
$603,333.00
Summary
Immune cells can play both beneficial and detrimental roles in cancer. We have devised a novel method to ‘tag’ immune cells inside tumours and follow their fate. Using this method we discovered that immune cells called T cells can leave primary tumours and migrate to lymph nodes. The aim of this project is to investigate the role of these tumour-egressing cells in tumour immunity and to determine whether their migration and function can be manipulated to improve anti-tumour therapies.
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.
Analysis Of Antigen Processing In Melanoma Cells, Its Influence On The Success Of Cancer Vaccination And Enhancement In A Combined-immunotherapy Xenograft Model Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$297,891.00
Summary
Cancer vaccines, an exciting new treatment option that aims to boost a patientÍs own immune system to fight a growing cancer, have shown great promise in developmental studies. Although these vaccines generate strong anti-cancer responses in the blood of treated patients, less than expected results have been observed in terms of increased patient survival. This project aims to understand how the cancer escapes recognition by the immune system and ways to enhance the effects of cancer vaccines.
Analysis Of Killer T Cell Geometry During An Anti-tumour Response
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Cancer is a major health problem around the world. Currently used treatment options of cancer have the drawback that they also damage healthy tissues. This limits the dosages that can be administered, frequently resulting in treatment failure. Anti-tumour killer T cells are a naturally occurring cell type that can cause tumour regression. In the present proposal, we explore how the efficiency of these cell-types can be further enhanced to induce rejection of progressing tumours.
The Role Of The Actomyosin Cytoskeleton In T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
T cells, specialised immune cells, are crucial in the defence against tumours. In order to reach cancerous target cells, T cells must enter tumour tissues from the blood stream and then effectively migrate in the extravascular space. This application aims to uncover the role of the cytoskeleton, a group of molecules driving cell shape change and motility, in the efficient execution of T cell anti-tumour function. These studies will aid the development of improved immunotherapies against cancer.
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 Role Of NK Cell Receptors In Tumor Immunity And Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$641,264.00
Summary
White blood cells lymphocytes have an important role to play in cancer immunity and the activity of some cancer therapies. Therapeutics that improve lymphocyte function in patient tumors are showing great promise. Yet, virtually nothing is known about one family of lymphocyte receptors that control function in cancer. Using relevant mouse models of cancer and patient tumors we now wish to assess the relative importance of this family of receptors in tumor immunity, therapy, and escape.
The Role Of The Transcription Factor Blimp-1 In Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$642,674.00
Summary
Regulatory T (Treg) cells function by suppressing immune system activity, ensuring that our immune system does not mount a response against our own tissue. In cancer, Treg cells suppress anti-tumour immunity, facilitating tumour growth. Recently we have identified a group of active Treg cells that may be the key drivers of immune response regulation. Our work will examine the role of these active Treg cells in tumour immunity, opening the door to more effective targeting of Treg cells in cancer.
Perforinopathy: Immune-disease Due To Defective Perforin Function
Funder
National Health and Medical Research Council
Funding Amount
$671,514.00
Summary
White blood cells called cytotoxic lymphocytes destroy cancerous cells using special toxic molecules. One of them, perforin, eliminates dangerous cells by punching holes in their membrane. Some individuals that lack perforin become seriously ill in their infancy. Others, that retain some perforin in their lymphocytes can live longer and are at higher risk of developing cancer. We will investigate the causes of partial loss of perforin function and explore novel drug therapies, which should addre ....White blood cells called cytotoxic lymphocytes destroy cancerous cells using special toxic molecules. One of them, perforin, eliminates dangerous cells by punching holes in their membrane. Some individuals that lack perforin become seriously ill in their infancy. Others, that retain some perforin in their lymphocytes can live longer and are at higher risk of developing cancer. We will investigate the causes of partial loss of perforin function and explore novel drug therapies, which should address the problem and restore immune function.Read moreRead less