B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody

J Pharmacol Exp Ther. 2010 Oct;335(1):213-22. doi: 10.1124/jpet.110.168062. Epub 2010 Jul 6.


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.

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Murine-Derived
  • Antibody-Dependent Cell Cytotoxicity
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • B-Lymphocytes / physiology*
  • Cell Proliferation / drug effects
  • Fucose / chemistry
  • Humans
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Transgenic
  • Protein Engineering
  • Rituximab


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Immunoglobulin G
  • Fucose
  • Rituximab