Strategies to overcome the KIR-KIRL-mediated inhibition of NK cells and to increase their antileukemic response. (A) KIR-KIRL interaction is blocked by a monoclonal antibody, which abolishes the inhibitory signal. (B) KIR-KIRL-mediated inhibition is overridden by the activation of the Fc-receptor (CD16), with an antibody directed against an antigen expressed on leukemic blasts. (C-D) A bispecific killer engager and a trispecific killer engager activate NK cells via the Fc-receptor against antigens expressed on leukemia cells. (E) CAR-NK cells directed against the CD19 antigen are depicted.