Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Breast cancer is the most common neoplasm affecting Canadian women. Although current therapies are having a definite impact on this illness, one-third of all women initially diagnosed with early stage breast cancer develop recurrent or metastatic breast cancer, which is presently incurable. Much effort is focused on improving targeted cellular therapy to selectively kill cancer cells and increase the survival rates of patients. The development of an effective immune-based cancer therapy, however, is complicated by mechanisms of "immune tolerance". Since tumours are derived from healthy tissues, they are tolerated by our immune system. In addition to selective deletion of immune cells that might attack normal host cells, active suppression by T regulatory (Treg) cells is also a major mechanism of immune tolerance. By promoting the development of Treg cells, cancers can evade the immune system. Therefore, the ability of Treg cells to down-regulate the immune response to tumour cells is a significant concern. Our research aims to determine whether antigen-presenting cells (APCs) that have been genetically-modified to boost immunity to breast cancer cells will result in undesirable development of Treg cells and/or stimulation of existing Treg cells. We will first develop methods to generate 2 different types of APCs (dendritic cells and B cells) in different stages of development, and then test whether in addition to stimulating anti-tumour T cells, they may also promote the development and/or function of Treg cells. We will also investigate if pre-existing Treg cells can impact the function of APCs. Our goal is to identify a population of APCs that can specifically stimulate anti-cancer T cell responses and simultaneously limit the function of suppressive Treg cells. If we are successful in this endeavour, our studies will enhance the efficiency of new cell-based anti-tumour vaccinations for women with breast cancer.