Differential in vivo effects of rituximab on two B-cell subsets in cynomolgus monkeys

Int Immunopharmacol. 2003 Oct;3(10-11):1477-81. doi: 10.1016/S1567-5769(03)00147-4.


Cynomolgus monkeys (Macaca fascicularis) are widely used animal models in biomedical research and have been used to study new therapeutics aimed at B-cell depletion. We have recently identified two different B-cell subsets in cynomolgus monkey, with the CD20lowCD40highCD21+ subset being phenotypically closer to human B cells and having a similar responsivness to anti-CD20 mAb, rituximab, in in vitro depletion assays. Here, we show that similar to in vitro findings CD20highCD40lowCD21- and CD20lowCD40highCD21+ cynomolgus monkey B cells differ significantly in their in vivo susceptibility to rituximab, as the low dose of 0.05 mg/kg of rituximab resulted in more than 70% depletion of the former B-cell subset and virtually no depletion of the latter B-cell subset. Our data suggest that for the B-cell-targeting anti-CD20 therapeutics, depletion of CD20lowCD40highCD21+ subset rather than depletion of all cynomolgus monkey B cells is more relevant to dose-efficacy projections for humans. In addition, we show that differential cell surface expression of CD80/CD86 costimulatory molecules on the two different cynomolgus monkey B-cell subsets is similar to that identified in rhesus monkeys, suggesting that our in vivo study may be relevant to other monkey models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / immunology
  • Antineoplastic Agents / pharmacology*
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • CD40 Antigens / immunology
  • Lymphocyte Depletion
  • Macaca fascicularis
  • Male
  • Receptors, Complement 3d / immunology
  • Rituximab


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • CD40 Antigens
  • Receptors, Complement 3d
  • Rituximab