Project 466802

Cancer affects a substantial portion of the Canadian population; however, a universal cure remains elusive. Recent approaches to cancer treatment have focused on T cells, an important type of immune cell that helps to attack cancerous and virally infected cells. A novel treatment approach, termed CAR-T cell therapy, involves re-engineering T cells to recognize and target tumours. While this approach has achieved remarkable success in treating blood cancers, the efficacy has been substantially reduced in patients with solid tumours, owing to the immunosuppressive nature of the tumour microenvironment. This phenomenon can be studied in animal models to a certain extent; however, the high costs and long duration of animal studies limits the capacity for iterative improvement of CAR-T cell design. The proposed work aims to develop a solid tumour-on-a-chip platform designed to evaluate CAR-T cell function. To provide a more accurate representation of the tumour microenvironment, this platform will modularly incorporate key immunosuppressive features, including dysregulated blood vessels and oxygen deprivation, such that the influence of each feature can be studied independently. This work will provide insight into how various immunosuppressive features in the tumour microenvironment contribute to CAR-T cell dysfunction, enabling the development of improved CAR-T cell therapies for solid tumour patients.