An engineered tri-specific natural killer (NK) cell engager (NKCE) containing specific antibodies targeting the tumor-associated antigen cluster of differentiation 123 (CD123), and the NK activating receptors natural cytotoxicity triggering receptor (NKp46; activating natural killer receptor p46) and CD16, with potential immunostimulating and antineoplastic activities. Upon administration of NKp46/CD16-based CD123-targeted NK cell engager SAR443579, the NKCE targets and binds to CD123 expressed on tumor cells and simultaneously binds, via the activating receptors NKp46 and CD16, to NK cells, thereby bringing CD123-expressing tumor cells and NK cells together. This stimulates the NK cells and results in the selective NK cell-mediated tumor cell lysis of CD123-expressing tumor cells. CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with both increased leukemic cell proliferation and aggressiveness.