TY - JOUR T1 - B-Cell Depletion In Vitro and In Vivo with an Afucosylated Anti-CD19 Antibody JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 213 LP - 222 DO - 10.1124/jpet.110.168062 VL - 335 IS - 1 AU - Ronald Herbst AU - Yue Wang AU - Sandra Gallagher AU - Nanette Mittereder AU - Ellen Kuta AU - Melissa Damschroder AU - Rob Woods AU - Daniel C. Rowe AU - Li Cheng AU - Kim Cook AU - Krista Evans AU - Gary P. Sims AU - David S. Pfarr AU - Michael A. Bowen AU - William Dall'Acqua AU - Mark Shlomchik AU - Thomas F. Tedder AU - Peter Kiener AU - Bahija Jallal AU - Herren Wu AU - Anthony J. Coyle Y1 - 2010/10/01 UR - http://jpet.aspetjournals.org/content/335/1/213.abstract N2 - The pan B-cell surface antigen CD19 is an attractive target for therapeutic monoclonal antibody (mAb) approaches. We have generated a new afucosylated anti-human (hu)CD19 mAb, MEDI-551, with increased affinity to human FcγRIIIA and mouse FcγRIV and enhanced antibody-dependent cellular cytotoxicity (ADCC). During in vitro ADCC assays with B-cell lines, MEDI-551 is effective at much lower mAb concentrations than the fucosylated parental mAb anti-CD19-2. Furthermore, the afucosylated CD19 mAb MEDI-551 depleted B cells from normal donor peripheral blood mononuclear cell samples in an autologous ADCC assay, as well as blood and tissue B cells in human CD19/CD20 double transgenic (Tg) mice at lower concentrations than that of the positive control mAb rituximab. In huCD19/CD20 Tg mice, both macrophage-mediated phagocytosis and complement-dependent cytotoxicity contribute to depletion with rituximab; MEDI-551 did not require complement for maximal B-cell depletion. Furthermore, extended B-cell depletion from the blood and spleen was achieved with MEDI-551, which is probably explained by bone marrow B-cell depletion in huCD19/CD20 Tg mice relative to the control mAb rituximab. In summary, MEDI-551 has potent B-cell-depleting activity in vitro and in vivo and may be a promising new approach for the treatment of B-cell malignancies and autoimmune diseases. ER -