Nonfucosylated anti-CD20 antibody potentially induces apoptosis in lymphoma cells through enhanced interaction with FcγRIIIb on neutrophils

被引:15
作者
Nakagawa, Tomoaki [1 ]
Natsume, Akito [1 ]
Satoh, Mitsuo [1 ]
Niwa, Rinpei [1 ]
机构
[1] Kyowa Hakko Kirin Co Ltd, Antibody Res Labs, Div Res, Machida, Tokyo 1948533, Japan
关键词
Immunotherapy; Rituximab; Nonfucosylated antibody; Neutrophil; Antibody-dependent cellular cytotoxicity; Apoptosis; DEPENDENT CELLULAR CYTOTOXICITY; NON-HODGKINS-LYMPHOMA; NATURAL-KILLER-CELLS; HUMAN B-CELLS; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; RITUXIMAB; EXPRESSION; RECEPTOR; COMPLEMENT;
D O I
10.1016/j.leukres.2009.10.029
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We demonstrate herein the augmentation of rituximab-mediated apoptosis in lymphoma cell lines by cross-linking with recombinant Fc gamma Rs, which is further enhanced by using a nonfucosylated variant of rituximab having strong Fc gamma RIII-binding capacity. Furthermore, we show that neutrophils can serve as physiological cross-linkers that augment anti-CD20-mediated apoptosis, as evidenced by (i) the neutrophil-augmented apoptosis was more profound for the nonfucosylated variant of rituximab and (ii) the mechanism depended on Fc gamma RIIIb but not on Fc gamma RIIa. Taken together, we suggest a potential antitumour mechanism of nonfucosylated anti-CD20 antibody by which antibody molecules are cross-linked through enhanced interaction with Fc gamma RIIIb in neutrophils. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:666 / 671
页数:6
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