Ashley Yang Rose Hills
Investigation of Therapeutic Efficacy of EGFRvIII-targeting CAR-NK cells against Glioblastoma in vitro and in vivo
Glioblastoma (GB) is the most common and aggressive brain tumor in adults, composed of a microenvironment that suppresses the defense function of T-cells and Natural Killer (NK) cells. Chimeric antigen receptors (CARs) have recently become a robust form of adoptive cell therapy, also known as cellular immunotherapy. Studies on GB treatment using CAR-NK cells have identified epidermal growth factor receptor (EGFRvIII) as a target which distinguishes GB cells from healthy brain cells. Currently, there is a lack of CAR-NK cell mouse models. My project will seek to fill the gaps by developing EGFRvIII-targeting CAR-NK cells to treat glioblastoma and to test whether CAR-NK cells have a better cytotoxic effect on killing tumor cells in vitro and solid tumors in vivo. The data from the mouse models will allow us to investigate the clinical aspect more closely and will show whether CAR-NK cells traffic to the tumor, persist in the tumor microenvironment, and can effectively eradicate the tumor. Understanding the mechanisms of CAR-NK cell therapy will hopefully provide more insight as to broadening the therapeutic use of these natural cytotoxic cells of the innate immune system.