Grant: Banting Postdoctoral Fellowship Program

A bone marrow transplant provides a patient with stem cells that will ultimately produce new immune cells capable of remedying diseases like immunodeficiency and cancer. These transplants can be dangerous because the recipient needs to undergo toxic chemotherapy or radiation to make room in their marrow for the donor's cells. Furthermore, it can be difficult to find a donor that is a close genetic match with the recipient. If the transplanted cells are not a sufficient match, they can attack the patient's healthy tissues. To avoid these risks, the goal of my project is to produce immune cells from pluripotent stem cells in the laboratory. Directly transplanting immune cells circumvents the need for dangerous chemotherapy or radiation. Creating immune cells from pluripotent stem cells also offers other important advantages. Unlike the cells found in bone marrow, pluripotent stem cells can be grown extensively outside of a patient. The ability to efficiently grow pluripotent stem cells in the laboratory makes them a renewable cell source that can easily be scaled up to meet patient needs. This property of self-renewal also means they are considerably more amenable to genetic modifications that can correct disease-causing mutations, improve cancer fighting properties or compensate for genetic mismatches between the donor and recipient. Others have shown that stem cells can be guided to become immune cells in the lab, but these prior methods required mouse cells to shepherd the stem cells down the right path. To avoid the requirement for these mouse cells, which are not compatible with downstream clinical use, I will genetically program the stem cells so that they can guide themselves down the path to becoming immune cells. By providing a renewable and clinically usable supply of genetically engineered immune cells, we aim to reduce the sizeable impact of cancer and immune disorders in Canada.