Grant: Project Grant

Immunocompromised individuals or cancer patients who have been treated with radiation and/or chemotherapy, as part of a bone marrow or hematopoietic stem cell transplant, are especially vulnerable to opportunistic 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, critically important T-cells remain absent or at low numbers for a long period after treatment, and if donor 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. Our laboratory has developed innovative systems that mimics thymus function and its ability to direct blood stem cells to become T-cells. Our preliminary data in aged mouse models show that mice injected with proT cells engraft the host thymus and develop greater reactivity and protection against a virus infection, with no sign of graft vs host disease. We plan to extend our 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, without graft vs. host disease, and enable faster recovery of immune function to fight infections and cancer relapse.