Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
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.
Molecular Pathways That Control Differentiation And Function Of Tissue-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$890,636.00
Summary
T cells residing in organs such as gut, liver or skin guard against infection and are critical for preventing tumour development. We found that the combined activities of two factors, Blimp1 and Hobit, are critical for the development of these so-called tissue-resident T cells. Using a series of new tools, we will identify how the molecular network required for the development of tissue-resident T cell is established. This may allow us to harness their critical functions in therapy.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.
Postnatal Germ Cells Are Controlled By FSH During 'minipuberty' At 3-6 Months, And Deranged By Cryptorchidism To Cause Seminoma And Infertility
Funder
National Health and Medical Research Council
Funding Amount
$813,739.00
Summary
This study will investigate the exciting possibility that the risk of cancer and infertility in adulthood in infants born with undescended testes might be obviated by understanding how primitive sperm cells behave in the postnatal testis. The study will define the key changes to the primitive sperm cells, including their timing and control by hormones, so surgery is done at the right time +/-accessory hormone treatment to optimise future sperm function for babies with undescended testes.
Understanding And Applying Macrophage-mediated Effects On Liver Progenitor Cells To Treat Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$628,109.00
Summary
As liver cancer risk correlates with increased liver stem/progenitor cell numbers, therapies that reduce their numbers will reduce cancer development. On the contrary, therapies to increase progenitor cell numbers will assist their use in cell therapy-based approaches or artificial liver devices to treat chronic liver disease. This project will determine how to use inflammatory cells to manipulate progenitor cell numbers.
A Novel Macrophage Lineage In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$772,857.00
Summary
Macrophages are an important haematopoietic cell type that has been implicated in inflammatory and cancerous diseases. In our preliminary work we have discovered a new macrophage subset, termed the perivascular macrophage, in breast cancer. The aim of this proposal is to investigate the origin of these cells, and the role they play in breast cancer. This will tell us how we might be able to manipulate the functions of these cells in order to curtail breast cancer progression.
Progenitor Origin And Regulation In Endometrial Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$847,583.00
Summary
The endometrium is the lining of the uterus and regenerates each month during a woman's reproductive years. Stem and progenitor cells in the endometrium are thought to be responsible for this regeneration. We have identified a genetic marker for stem and progenitor cells in the endometrium of mice and will use this to understand endometrial regeneration. This work will address infertility as well as overactive endometrial growth in diseases such as endometriosis and endometrial cancer.
Mab Immunotherapies For Myeloid Leukemia Patients With Germline Or Somatic RUNX1 Mutations.
Funder
National Health and Medical Research Council
Funding Amount
$766,995.00
Summary
This proposal presents preliminary evidence and proposes to confirm that 2 cell surface molecules, CD11a (ITGAL) and IL3RA (CD123) are direct (probably repression) targets of RUNX1 in HSCs, and are dysregulated in RUNX1 mutated AML. Monoclonal antibody therapies that target these two surface molecules have already passed different clinical trial phases for different diseases. We plan to show these antibodies are effective in RUNX1 positive AML in preclinical models and then clinical trials.