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In this study, we aimed to address this unmet medical need by choosing the B\u2010cell activating factor receptor (BAFF\u2010R) as a promising target for CAR design against CLL. BAFF\u2010R is essential for B\u2010cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF\u2010R CAR T\u2010cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19\u2010knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF\u2010R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient\u2010derived CAR T cells against autologous tumor cells. 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