Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20

Blood. 1994 Jan 15;83(2):435-45.


Murine monoclonal antibody 2B8 specifically recognizes the CD20 phosphoprotein expressed on the surface of normal B lymphocytes and B-cell lymphomas. The light- and heavy-chain variable regions of 2B8 were cloned, after amplification by the polymerase chain reaction, into a cDNA expression vector that contained human IgG1 heavy chain and human kappa-light chain constant regions. High-level expression of chimeric-2B8 antibody (C2B8) was obtained in Chinese hamster ovary cells. Purified C2B8 exhibited antigen binding affinity and human-tissue reactivity similar to the native murine antibody. In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity. Infusion of macaque cynomolgus monkeys with doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater than 98% depletion of peripheral blood (PB) B cells and 40% to 70% depletion of lymph node B cells. Recovery of PB B cells usually started at 2 weeks after treatment and required 60 to greater than 90 days to reach normal levels. As much as 95% depletion of B cells in peripheral lymph nodes and bone marrow was observed following weekly injections of 16.8 mg/kg antibody. No toxicity was observed in any of the animals. These results offer the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibody Specificity
  • Antigens, CD / immunology*
  • Antigens, CD20
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • B-Lymphocytes / physiology*
  • Base Sequence
  • CHO Cells
  • Cricetinae
  • Humans
  • Lymph Nodes / cytology
  • Lymphocyte Depletion*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Recombinant Fusion Proteins / immunology*


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD20
  • Antigens, Differentiation, B-Lymphocyte
  • Recombinant Fusion Proteins