A human, tetravalent, bispecific immunoglobulin G1 (IgG1)-single chain variable fragment (scFv) fusion antibody targeting both the tumor-associated antigen (TAA) CD123 and the human low affinity immunoglobulin G (IgG) Fc region receptor IIIA (FCGR3A; CD16A), with potential immunomodulating and antineoplastic activities. Upon administration, anti-CD123/CD16A bispecific antibody AFM28 simultaneously targets and binds to CD16A expressed on natural killer (NK) cells and macrophages, and to CD123 on CD123-expressing tumor cells, thereby selectively cross-linking CD123-expressing tumor cells with NK cells and macrophages. This may result in NK cell and macrophage activation, induce antibody-dependent cellular cytotoxicity (ADCC), and eventually causes tumor cell lysis. CD123 is overexpressed in a variety of hematological malignancies; its expression is low or absent in normal hematopoietic progenitors and stem cells. CD16A is specifically expressed on the surface of NK cells and macrophages.