The Therapeutic CD38 Monoclonal Antibody Daratumumab Induces Programmed Cell Death via Fc{gamma} Receptor-Mediated Cross-Linking [IMMUNOTHERAPY AND VACCINES]

Emerging evidence suggests that FcR-mediated cross-linking of tumor-bound mAbs may induce signaling in tumor cells that contributes to their therapeutic activity. In this study, we show that daratumumab (DARA), a therapeutic human CD38 mAb with a broad-spectrum killing activity, is able to induce programmed cell death (PCD) of CD38⁺ multiple myeloma tumor cell lines when cross-linked in vitro by secondary Abs or via an FcR. By comparing DARA efficacy in a syngeneic in vivo tumor model using FcR-chain knockout or NOTAM mice carrying a signaling-inactive FcR-chain, we found that the inhibitory FcRIIb as well as activating FcRs induce DARA cross-linking–mediated PCD. In conclusion, our in vitro and in vivo data show that FcR-mediated cross-linking of DARA induces PCD of CD38-expressing multiple myeloma tumor cells, which potentially contributes to the depth of response observed in DARA-treated patients and the drug's multifaceted mechanisms of action.

from #ENT via xlomafota13 on Inoreader http://ift.tt/29QzB3N
via IFTTT