We show that redirecting NK cells against cancer targets through binding to NKp46 circumvents the CD64-mediated inhibition of ADCC, with CD123-NKCE active and superior to Fc-engineered ADCC-enhancing IgG1 antibody targeting the same antigen, in vitro, ex vivo and in vivo, whatever the CD64 status of the target cells. Here, IL3RA is linked to cancer.