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Effect of anti‐CD20 monoclonal antibody, Rituxan, on cynomolgus monkey and human B cells in a whole blood matrix
Author(s) -
Vugmeyster Yulia,
Howell Kathy,
Bakshl Anahid,
Flores Clarissa,
CanovaDavis Eleanor
Publication year - 2003
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.10030
Subject(s) - cd20 , cd40 , monoclonal antibody , b cell , ex vivo , immunology , antibody , flow cytometry , in vivo , monoclonal , biology , in vitro , microbiology and biotechnology , cytotoxic t cell , biochemistry
Background Cynomolgus monkeys are widely used animal models in biomedical research. The differences between cynomolgus monkey and human B cells are not completely understood. However, these differences are of crucial importance for interpretation of data from studies on new therapeutic agents aimed at B‐cell depletion, such as anti‐CD20 monoclonal antibodies. Methods Multicolor fluorescence‐activated cell sorting analysis of peripheral blood B cells was performed on samples treated ex vivo with the anti‐CD20 therapeutic monoclonal antibody, Rituxan, in a whole blood matrix. Results In contrast to humans, cynomolgus monkeys had two distinct B‐cell subsets, CD20 high CD40 low CD21 − and CD20 low CD40 high CD21 + . These B‐cell subsets had a 2.5‐fold difference in the EC 50 for Rituxan binding and differed significantly in their in vitro susceptibility to Rituxan depletion. Human B cells were similar to the CD20 low CD40 high CD21 + cynomolgus monkey B cells with regard to their EC 50 for Rituxan and response to Rituxan in a whole blood matrix assay. CD21 was upregulated, whereas CD40 was downregulated at incubation with Rituxan in the CD20 low CD40 high CD21 + monkey and human B cells in a concentration‐dependent manner. Conclusions These findings have direct implications for in vivo studies of therapeutic agents that target B cells in cynomolgus monkeys and for extrapolation of the results to humans. In addition, our data are consistent with the model in which CD20, CD21, and CD40 exist in a supramolecular complex that is affected by anti‐CD20 monoclonal antibodies. Cytometry Part A 52A:101–109, 2003. © 2003 Wiley‐Liss, Inc.