Strategies for improving NK cell–based therapy. NK cells used in therapy can be improved by increasing effector responses, enhancing targeting, decreasing suppression, and improving in vivo functional persistence. ECD, extracellular domain; HCW9201, IL-12/IL-15/IL-18 receptor agonist; HCW9206, IL-7/IL-15/IL-21 receptor agonist; N-803, IL-15 receptor super agonist; mbIL-15-Rα, membrane-bound IL-15 receptor associated with high-affinity IL-15 receptor alpha subunit; HCW9218, IL-15 receptor agonist fused with TGF-β trap; BiKE/TriKE, bi- or tri-specific killer engagers, respectively; TM/ICS, transmembrane/intracellular signaling domain.