Juan Carlos Zuniga-Pflucker, PhD, Technology Impact Award Recipient Sunnybrook Research Institute Area of Research: All Cancers Cancer patients who have been treated with radiation or chemotherapy are especially vulnerable to viral and bacterial infections, in addition to cancer relapse. These treatments weaken the immune system through depletion of white blood cells. While most subsets of white blood cells recover early, the critical T cells remain absent or low for a long period after treatment and if T cells are included in a bone marrow transplant, then it may lead to complications such as graft vs. host disease. The delay in T cell recovery relates to the organ where T cells develop, the thymus, as it degenerates with age and is further damaged by radiation and chemotherapy. Dr. Zuniga-Pflucker’s lab has developed innovative systems that mimic the thymus’ ability to direct blood stem cells to become T cells. They involve presentation of a signaling protein called Delta to cultured blood stem cells to trigger the activation of its receptor, Notch, and conversion of blood stem cells into T cells. The novel system he and his team developed, called DL4-microbeads, has many potential advantages including: 1) absence of any cell-based or animal by-products and thus readily adaptable to clinical use; 2) provision of a simple and elegant path to turn stem cells into progenitor T cells in a scalable way; and, 3) progenitor T cells home to the thymus and convert to mature T cells that are host-tolerant. His preliminary data in an aged mouse model show mice injected with progenitor T cells engraft the host thymus and develop greater reactivity and protection against a virus infection, with no sign of graft vs host disease. He plans to extend these findings to other infectious agents and model cancer cells. The impact of rapid and safe T cell recovery in immune-compromised patients, especially in the elderly, after radiation or chemotherapy would be dramatic. It would lead to improved patient health through faster recovery of immune function to fight infections and cancer relapse without graft vs. host disease. Projects and Grants Progenitor T-cell generation in culture for re-establishing T-cell immunity and targeted immunotherapies Sunnybrook Research Institute | All Cancers | 2021
