Grant: Project Grant

Ovarian cancer is a challenging disease with unacceptably high mortality. Despite this, about 30% of patients "beat the odds" and live for many years after treatment. Why do some patients do so well? In the past decade, it has become well established that many long-term survivors of ovarian cancer exhibit a strong immune response against their tumor, providing a plausible explanation for their favourable outcome. We have shown that the immune response against cancer involves collaboration between several types of white blood cells, including killer T cells and antibody-producing B cells. With better understanding of the immune response, it will be possible to design new treatments that enhance tumor immunity and increase patient survival. In this study, we will investigate the mechanisms by which B cells work with other immune cells to recognize and attack cancer. In Aim 1, we will use state-of-the-art genomics methods to probe the molecular properties of individual B cells and associated immune cells isolated from 50 human ovarian cancer specimens, giving us unprecedented insights into the inner workings of the immune system in patients. In Aim 2, we will isolate the antibodies produced by 200 or more B cells from ovarian tumours and use these to further decipher the mechanisms by which B cells amplify the immune response to cancer. The data, tools and knowledge arising from this study will help us design new immunotherapies that fortify the patient's natural defense mechanisms, leading to increased survival. Through local and national initiatives, our team is exceptionally well positioned to translate our findings into early stage clinical trials of promising new immunotherapy strategies for ovarian cancer patients in Canada.