Efficacy and mechanism of the anti-CD38 monoclonal antibody Daratumumab against primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare, aggressive B cell non-Hodgkin's lymphoma of the body cavities with malignant effusions. The prognosis is poor, and no optimal treatment has been established. CD38 is a type II transmembrane glycoprotein known to overexpress in multiple myeloma (MM). Daratumumab (DARA), a human CD38-targeting monoclonal antibody (mAb), is approved for MM treatment. In this study, we found expression of CD38 on PEL cells and assessed the anti-PEL activity of DARA. We found that both KHYG-1 and N6 (CD16-transfected KHYG-1) NK cell lines showed direct killing activity against PEL cells with induction of CD107a, and NK-mediated cytotoxicity by N6NK (CD16+) cells increased with DARA treatment. We confirmed direct NK activity and antibody-dependent cell cytotoxicity (ADCC) by expanded NK cells, indicating that DARA has high ADCC activity. We elucidated the antibody-dependent cell phagocytosis (ADCP) by using human monocyte-derived macrophages (MDMs) and mouse peritoneal macrophages. DARA also showed potent complement-dependent cytolysis (CDC) toward PEL. DARA also induced PEL cell death in the presence of a cross-linking antibody. Moreover, treatment with DARA inhibited tumor growth in a PEL xenograft mouse model. These results provide preclinical evidence that Ab targeting of CD38 could be an effective therapeutic strategy for the treatment of PEL.