Search results for: Mouse Anti-Human CD19 (pan B-cells) Antibodies
#20605905 2010/07/06 To Up
B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody.
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.Ronald Herbst, Yue Wang, Sandra Gallagher, Nanette Mittereder, Ellen Kuta, Melissa Damschroder, Rob Woods, Daniel C Rowe, Li Cheng, Kim Cook, Krista Evans, Gary P Sims, David S Pfarr, Michael A Bowen, William Dall'Acqua, Mark Shlomchik, Thomas F Tedder, Peter Kiener, Bahija Jallal, Herren Wu, Anthony J Coyle
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