Project 467038

Our immune systems can recognize foreign invaders such as viruses and bacteria resulting in the generation of immune responses. In the context of cancer, many of these diseased cells express antigens that are not normally found in the body causing these abnormal cells to be classified as foreign. In response, the immune system produces killer T cells specific for the cells expressing these foreign antigens with the hope of killing off the population. Unfortunately, cancers tend to mutate quickly causing changes in their antigen repertoires and a loss of recognition by these killer T cells. Attempts have been made to boost these killer T cell responses by extracting tumor antigens and feeding them directly to the cell type that turns them on, called dendritic cells. This approach however still leaves the door open to immune escape since it relies only on a finite set of antigens. As a result, another approach is being employed where a specific subset of these dendritic cells generated using antiviral factors is injected directly into tumor lesions. When combined with other cancer drugs, this approach has been proven to generate new populations of cancer specific killer T cells in patients. With the properties of this dendritic cell subset as a starting point, this project aims to engineer dendritic cells to be even more potent. Using viruses, these cells will be genetically engineered to express receptors that will allow them to directly take bites of cancer cells and extract tumor antigens more effectively. Using mouse models, the goal is to determine whether this could be a new effective immune cell therapy for treating cancer based on the ability of this platform to induce strong killer T cell responses and eliminate the abnormal cell populations.