期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 3, 期 10-11, 页码 1477-1481出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S1567-5769(03)00147-4
关键词
B cells; anti-CD20; rituximab; nonhuman primates
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 CD20(low)CD40(high)CD21(+) 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 CD20(high)CD40(low)CD21(-) and CD20(low)CD40(high)CD21(+) 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 CD20(low)CD40(high)CD21(+) 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. (C) 2003 Elsevier B.V. All rights reserved.
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