Chimeric Antigen Receptors (CARs) are engineered proteins that can be used in a therapeutic capacity when expressed by an immune cell (e.g., a T cell). Specifically, CARs comprise a targeting domain (such as an antibody or binding fragment thereof) as well as domains that activate immune cells. By selecting a targeting domain that binds to a protein that is selectively expressed on a cancer cell, it is possible to target immune cells to the cancer cells. Upon binding to the target cell, the immune cells are activated, leading to the destruction of the cancer cell. This therapeutic approach holds great promise, as evidenced by the recent FDA-approval of CAR-T cell therapies, KYMRIAH and YESCARTA, both of which target CD19.