Using Genetically Manipulated Mice To Study The Pathophysiologic Consequences Of Castration-induced Prostatic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
Prostate cancer is the second leading cause of cancer death among Australian men. The disease is incurable once it spreads beyond the confines of the prostate gland. Hormonal treatments can keep the cancer at bay for a number of years until they are no longer effective. Hormonal treatments cause shrinkage of prostate cancer because they interfere the function of the male hormone, testosterone, which encourages growth of prostate cancer. Hence, there is a need for other treatments that may improv ....Prostate cancer is the second leading cause of cancer death among Australian men. The disease is incurable once it spreads beyond the confines of the prostate gland. Hormonal treatments can keep the cancer at bay for a number of years until they are no longer effective. Hormonal treatments cause shrinkage of prostate cancer because they interfere the function of the male hormone, testosterone, which encourages growth of prostate cancer. Hence, there is a need for other treatments that may improve the quality of life and survival of prostate cancer patients. It appears that a cancer patient can make immune cells known as T cells, which can recognise his own tumour but which are prevented from destroying the tumour. Using a mouse model of prostate cancer, we wish to understand how prostate tumours act to prevent immune destruction in circumstances that are common to the treatment of human prostate cancer. For example, hormonal treatments produce dead prostate cancer cells that will be cleared by the body's professional scavenger cells in a way that suppresses an active immune response against the tumour. To learn how the removal of dead cells suppresses the immune response, we propose to perturb the normal clearance of dead prostate cells by at least two means. First, we will study mice that have an inherited deficiency in the removal of dead cells. Second, these mice will be given a growth factor to produce an excess of immune stimulating cells known as dendritic cells in the prostate gland. The dendritic cell is the main type of cell that initiates immune responses. We will investigate whether the greater number of dendritic cells, which were put into the prostate gland by the growth factor, can remove the dead prostate cells in a way that excites rather than suppresses the anti-tumour immune response. Positive results obtained from these studies may lead to the design of new treatments for advanced prostate cancer.Read moreRead less
The Role Of CD4+ T Cells In The Tumour Killing By CD8+ Memory T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wi ....It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wish to study the mechanism of how CD8+ memory T cells get activated to cancer killer cells by the CD4+ T helper cells. This information will help us to design better immunotherapies for cancer patients.Read moreRead less
IMMUNOTHERAPY OF MELANOMA WITH DENDRITIC CELL VACCINES
Funder
National Health and Medical Research Council
Funding Amount
$496,980.00
Summary
Melanoma is a skin cancer which continues to increase in incidence in Australia. It is a significant cause of morbidity and mortality because of its tendency to spread from skin to other body sites. It is largely resistant to chemotherapy. Immunological approaches to its treatment hold promise but there is a need to develop more effective vaccines to assist in treatment. Preliminary studies suggest that injection of dendritic cells primed with melanoma antigens induce strong immune responses and ....Melanoma is a skin cancer which continues to increase in incidence in Australia. It is a significant cause of morbidity and mortality because of its tendency to spread from skin to other body sites. It is largely resistant to chemotherapy. Immunological approaches to its treatment hold promise but there is a need to develop more effective vaccines to assist in treatment. Preliminary studies suggest that injection of dendritic cells primed with melanoma antigens induce strong immune responses and regression of melanoma. If this can be confirmed it will represent a significant advance in treatment of the disease. The studies in the proposal are to investigate whether a new form of treatment based on immunisation with dendritic cells sensitised with tumour antigens will prove to be more effective than existing treatments. Dendritic cells are responsible for stimulating immune responses and are grown from the patient's blood. They are then sensitised with tumour antigens and injected into the lymph nodes of the patient. The study will also measure immune responses during the immunisation procedure and assess whether these measures can predict clinical responses in the patient. If the study is successful in its objectives it will assist in development of more effective treatment of melanoma.Read moreRead less