CD45-Directed CAR-T Cells with CD45 Knockout Efficiently Kill Myeloid Leukemia and Lymphoma Cells In Vitro Even after Extended Culture

BACKGROUND: CAR-T cell therapy has shown impressive results and is now part of standard-of-care treatment of B-lineage malignancies, whereas the treatment of myeloid diseases has been limited by the lack of suitable targets. CD45 is expressed on almost all types of blood cells including myeloid leukemia cells, but not on non-hematopoietic tissue, making it a potential target for CAR-directed therapy. Because of its high expression on T and NK cells, fratricide is expected to hinder CD45CAR-mediated therapy. Due to its important roles in effector cell activation, signal transduction and cytotoxicity, CD45 knockout aimed at preventing fratricide in T and NK cells has been expected to lead to considerable functional impairment. METHODS: /CD19CAR-T cells was studied using proliferation as well as short- and long-term cytotoxicity assays. RESULTS: /CD19CAR-T cells showed no differences from those of their CD45-positive counterparts in vitro. CONCLUSIONS: /CD45CAR-T cells might, for example, be useful as part of conditioning regimens prior to stem cell transplantation.