Tumour-associated Macrophages (TAMs) And Their Role In Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$72,537.00
Summary
Tumour-associated macrophages (TAMs) have been implicated in breast cancer spread. Tumour cell behaviour is influenced by the surrounding environment. This study will determine the relationship of TAMs to other cell populations, if the expression of the enzyme, u-PA, in non-tumour cells within the tumour environment is important for breast cancer spread, and whether TAM precursor white blood cells home to the primary tumour and-or to the site of tumour spread before the arrival of tumour cells.
Although the immune system has the ability to reject tumours, this sometimes does not occur, leading to cancer. There are many different types of cells that make up the immune system, including some which respond very early, called natural killer (NK) and NKT cells. These cells are the first line of defence against some tumours, although we do not understand how they recognise and respond to tumour cells. The aim of this project is to investigate the functional importance of both NK and NKT cell ....Although the immune system has the ability to reject tumours, this sometimes does not occur, leading to cancer. There are many different types of cells that make up the immune system, including some which respond very early, called natural killer (NK) and NKT cells. These cells are the first line of defence against some tumours, although we do not understand how they recognise and respond to tumour cells. The aim of this project is to investigate the functional importance of both NK and NKT cells in response to a range of different tumour types, including melanoma (skin cancer), lung carcinoma, breast carcinoma and sarcoma (connective tissue tumour). We will test the importance of each of these subsets by injecting these tumours into mice that have specific deficiencies in NK and-or NKT cells. If the NK or NKT cells are important, the tumours should grow more effectively when these immune cells are absent. We will also be able to put NK and-or NKT cells back into the mice to show directly that they are responsible for tumour rejection. Using a modification of this cell transfer approach, we will be able to inhibit special molecules that are normally produced by these cells that help them interact with other cells, and also help them attack the tumour cells. Collectively, the approaches outlined in this application allow us to determine which types of cells are important in response to a broad range of different tumour types, and also should tell us how these cells are able to attack the tumours. This information will be invaluable for the development of new strategies to use the patients immune system to attack cancer (known as immuno-therapy).Read moreRead less
Regulatory Mechanisms Of Antibody Cytotoxicity For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$566,087.00
Summary
Use of antibodies for cancer therapy, where a protein is made in the laboratory to recognize and act on cancer cells that have a target antigen, has emerged as an important therapeutic area in oncology. The lewis-y (Ley) antigen is found in over 70% of epithelial cancers. We have developed an antibody against Ley (hu3S193) which can target cancer cells. Our research is aimed at developing optimal cancer cell killing by our anti-Ley antibody.
WHAT IS THE RELATIVE ROLE OF TNF-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) IN TUMOR IMMUNITY?
Funder
National Health and Medical Research Council
Funding Amount
$85,660.00
Summary
Programmed cell death is a physiological process integral to the development and functioning of the immune system. A better understanding of the cellular effector cells and molecules that mediate cell death will provide valuable insight into designing better immunotherapeutic treatments of cancer. Members of the tumor necrosis factor (TNF) family of hormones and receptors are critically involved in the process of cell death. Within this family, several members have been well characterised and th ....Programmed cell death is a physiological process integral to the development and functioning of the immune system. A better understanding of the cellular effector cells and molecules that mediate cell death will provide valuable insight into designing better immunotherapeutic treatments of cancer. Members of the tumor necrosis factor (TNF) family of hormones and receptors are critically involved in the process of cell death. Within this family, several members have been well characterised and their functions ascribed. Some play an important role in the maintenance of immune cells , others in the movement of immune cells and organisation of lymphoid tissues. This proposal seeks to define the function of the recently discovered TNF-related apoptosis-inducing ligand (TRAIL). TRAIL mediates cell death of cancerous cells in culture but does not kill most normal tissues. This specificity for diseased tissue makes TRAIL a very promising candidate as an anti-tumor therapeutic. Until recently, very little was known regarding the natural physiological role of TRAIL. We have recently described the expression of TRAIL on liver natural killer cells and the anti-tumor activity of TRAIL against primary tumors and metastases. Importantly, TRAIL function appears to be regulated by an inflammatory mediator called interferon. We now wish to explore the role of TRAIL in tumor immunotherapies and tumor surveillance that requires interferon.Read moreRead less