Snap Shot of Research @ The DRC
IROC - Immune Response to Ovarian Cancer
Ovarian cancer remains a significant clinical problem. Recently, several independent studies have indicated that the immune system may play a significant role in determining clinical outcomes. Specifically, three groups have shown that women whose tumours have significant infiltrates of CD8+ ″killer″ T cells, with low numbers of CD4+ ″regulatory″ T cells, have a more favourable prognosis after standard treatments compared to women whose tumours have negligible T cell infiltrates. If we could better understand this immune response, and devise ways to enhance it in all women, we may be able to improve survival rates for this challenging disease. We propose to capitalize on our unique local strenths by assembling researchers from the DRC team with gynecological surgeons, pathlogists, and medical oncologists from the greater Victoria area.Principal researchers working on this are Dr. Brad Nelson, Dr. John Webb, Dr. Peter Watson, Dr. Elissa McMurtrie, Dr. Grant MacLean, and Dr. Nick Van Westhuisen.
Early Detection Projects
For many types of cancer, it is easier to treat and cure the cancer if it is found early. There are many different types of cancer, but most cancers begin with abnormal cells growing out of control, forming a lump or tumour. The tumour can continue to grow until the cancer begins to spread to other parts of the body. If the tumour can be found while it is still small and localized, it can often be cured by surgery and other standard treatments. The Deeley Research Centre′s Antibody Research Unit (ARU), is collaborating with a group of leading scientists from the United States to develop a rapid and accurate immunoassay that will detect ovarian cancer at an early stage, when it is still highly curable. Here at the DRC, our role involves the evaluation of potential biomarkers, their production as recombinant proteins, and the generation of antibodies with the goal of creating immuno-assays. For more info on the Canary Project, please see the Canary Foundation website: 
Canary Foundation
Research staff working on this project are Dr. Brad Nelson, Xiaobo Duan, Rob Sahota, and Sarah Chalk .
T Cell Therapy of Breast Cancer and Ovarian Cancer
T cells are a type of white blood cell that are very effective at killing abnormal cells in the body, including virally infected cells or cancerous cells. T cell therapy is currently being used in clinical trials for several different cancers and is very beneficial for some but not all patients. We have developed models of breast and ovarian cancer that allows us to precisely analyze the interactions that occur between T cells and tumours. In these models, we are able to eliminate about 30% of breast cancer and 80% of advanced ovarian cancers with T cells alone. We are using these models to learn how similar results might be achieved in breast cancer patients in future clinical trials.Research staff working on this project are Dr. Brad Nelson, Katy Milne, and Michele Martin.
Molecular & Pathological Mechanisms of Breast Cancer Progression
Probably the single most significant aspect of breast cancer progression is the transition from a localized tumour within the breast duct to a tumour capable of spreading beyond the breast to influence vital organs. Our lab focuses on identifying the molecular alterations that are functionally associated with this transition. The ultimate goal of this work is to identify effective targets for breast cancer therapy.
Research staff working on this project are Dr. Peter Watson, Josh Wang, and Rebecca Barnes.
Immune Response to Cancer
We are currently investigating four different types of cancer to determine the role of the immune system in the body′s fight against cancer. We are first trying to understand how standard treatments for cancer such as surgery, radiation and chemotherapy affect the patient′s immune response to their tumour. We are also trying to identify tumour proteins that are recognized by the immune system and could potentially serve as new targets for immune−based treatments. Our ultimate goal is to harness the power of the immune system to help fight cancers more effectively. The four studies underway are:
Prostate cancer
We have determined that hormone therapy and radiation therapy cause an immune response in up to 30% of prostate cancer patients. We are now trying to determine whether these patients have a better outcome and whether or not we can boost the immune system to enhance these outcomes. We are also trying to find markers on cancer cells that are specific to prostate cancer which would allow us to design immune-based therapies that selectively target the cancerous cells.
Research staff working on this project are Dr. Brad Nelson, Nancy Nesslinger.
Multiple Myeloma
Myeloma is a type of cancer in which one type of white blood cell (the plasma cell) grows continuously to form a tumour in the bone marrow. Our goal is to identify potential therapeutic markers on myeloma cells and, once identified, develop an anticancer antibody to defeat cancer cell growth. Research staff working on this project are Xiaobo Duan and Melanie Mawer.
Lymphoma
Non-Hodgkin Lymphoma is the fifth most common type of cancer in Canada. Many patients live with measurable disease for years with no evidence of disease progression and it is thought that this may be a result of patients mounting active anti-tumour immune responses. In support of this idea, recent studies where lymphomas were examined for the presence of tumour-infiltrating immune cells concluded that patient survival is positively correlated to the density of T cell infiltration in tumour tissue and negatively correlated to infiltration by macrophages. Despite these promising findings, the precise T cell subsets that underlie favourable outcomes have not been defined, nor have the relevant target antigens been identified. We are currently recruiting lymphoma patients in order to address these questions. The long-term goal of this project is to design and launch a phase I clinical immunotherapy trial of a T cell-based therapy for lymphoma.
Research staff working on this project are Dr. Brad Nelson and Dr. Julie Nielsen.
Identification of metabolic targets for immunetherapy
The focus of these studies is to understand how tumor metabolism and cell survival pathways affect oncogenesis and the immune response to cancer. Because all cells need to capture and use nutrients to grow and divide, it stands to reason that tumors must do this at an accelerated rate compared to normal cells. Recent work has shown that specific enzymes are preferentially expressed in tumors compared to normal tissues. Therefore, we are attempting to identify which metabolic enzymes and pathways are key for tumor growth and survival so that therapies can be developed to target and kill malignant cells with this type of abnormal metabolic phenotype.
Research staff working on this project are: Dr. Julian Lum, Alec Watson, Shabab Ali, Misha Horkoff
Understanding T cell responses to tumors
We are seeking to answer a simple question as to why the immune system fails to eliminate growing tumors? As tumors expand, their environment often becomes exhausted of all available nutrients. Immune cells which arrive from distant sites to kill tumors are also exposed to these nutrient-depleted surroundings and ultimately die. This is a major problem for developing adoptive T cell therapies for cancer. We want to learn how to promote immune cell survival to enhance our natural defenses against cancer by immunotherapy approaches.
Research staff working on this project are: Dr. Julian Lum, Katey Townsend
The role of autophagy in cancer progression and cancer stem cells
Despite the advent of modern cancer drugs, we know from patient studies that many individuals will experience tumor relapse. Many researchers believe this event is caused by outgrowth of a “cancer stem cell“. Autophagy is a specialized process by which cells can survive for long periods when they are exposed to cellular stress. Autophagy recycles resources in the cell to help maintain energy levels that are necessary for survival. Because chemotherapies/radiation and other anti-cancer drugs cause cellular stress, cells undergoing autophagy will escape the toxic effects of these drugs. We are studying whether cancer stem cells in ovarian cancer use autophagy to promote their survive and whether inhibition of autophagy can reduce tumor replase.
Research staff working on this project are: Dr. Julian Lum, Jaeline Briggs, Jill Brandon, Luke Hughson
The Histology Lab− Taking a Closer Look at Cancer
Histology− the study of tissues − is an essential tool in the diagnosis and study of cancer. Techniques are used to look at tumours at the tissue level to understand their structure and the cellular composition. Witness on a microscopic scale the battle between immune system cells and tumours. Research staff for this project is Katy Milne.
High School Programs
The High School Programs have been designed to offer local high school students and BC teachers the opportunity to explore cancer research at the front lines. Each summmer 4 students are selected for an 8−week Internship Program where they work side−by−side with DRC scientists. In our Outreach Program, these interns along with the outreach leaders then take their knowledge to local high schools and stage half−day molecular biology labs and lectures. BC Teachers are given an opportunity each fall to come to DRC and participate in sessions lead by leading resident Doctors and Researchers to learn about the latest cancer treatment developments and research projects. In addition to this, teachers will be given information about programs and resources offered at the BCCA that may be of help in dealing with those affected by cancer.Please contact Ann-Marie Braithwaite, Program Manager, for more details.
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