Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical 
development for the treatment of multiple myeloma (MM). The potential for IgG1 
antibodies to induce macrophage-mediated phagocytosis, in combination with the 
known presence of macrophages in the tumor microenvironment in MM and other 
hematological tumors, led us to investigate the contribution of 
antibody-dependent, macrophage-mediated phagocytosis to DARA's mechanism of 
action. Live cell imaging revealed that DARA efficiently induced 
macrophage-mediated phagocytosis, in which individual macrophages rapidly and 
sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse 
and human macrophages was also observed in an in vitro flow cytometry assay, 
using a range of MM and Burkitt's lymphoma cell lines. Phagocytosis contributed 
to DARA's anti-tumor activity in vivo, in both a subcutaneous and an intravenous 
leukemic xenograft mouse model. Finally, DARA was shown to induce 
macrophage-mediated phagocytosis of MM cells isolated from 11 of 12 MM patients 
that showed variable levels of CD38 expression. In summary, we demonstrate that 
phagocytosis is a fast, potent and clinically relevant mechanism of action that 
may contribute to the therapeutic activity of DARA in multiple myeloma and 
potentially other hematological tumors.