Neufeld, Luke

Project title: Improving T Cell Therapy for Cancer

Department: Biochemistry and Microbiology

Faculty supervisor: Dr. Brad Nelson

"This project aims to improve the effectiveness of Adoptive Cell Therapy (ACT), a new treatment that bolsters the patient’s immune response against their cancer through the infusion of large numbers of tumour-reactive T cells. Despite the great clinical success of ACT in some settings, there remain significant challenges that limit the effectiveness. In particular, there is a need to develop in vitro T cell expansion protocols that yield fit and active T cells rather than exhausted, terminally differentiated T cells. Traditional T cell expansion protocols use high concentrations of the T cell growth factor Interleukin-2. While this yields high numbers of T cells, they are often near the end of their functional lifespan. We hypothesize that using different combinations of growth factors that promote the formation of long-lived “memory” T cells will result in a less terminally differentiated product that is better suited to recognize and attack cancer when infused back into the patient’s bloodstream. Specific populations of T cells from the product will be classified based on their T-cell receptor variable β chain (TCR Vβ), which examines population clonality. T cell expansion products will then be analyzed by flow cytometry to determine how memory and exhaustion phenotypes vary among specific TCR Vβ populations. T cell expansion products will also be tested for reactivity against primary tumour samples. By evaluating different growth factor combinations, we hope to create an improved protocol that yields more potent T cells for use in ACT, leading to better patient outcomes."