Chao Debra T, Ma Xiaohong, Li Olga, Park Hyunjoo, Law Debbie
Research Department, PDL BioPharma, Redwood City, California 94063, USA.
Immunol Invest. 2009;38(1):76-92. doi: 10.1080/08820130802608238.
Several low- or non-FcR binding anti-human CD3 monoclonal antibodies have been under investigation for the treatment of autoimmune diseases. To model the mechanism of action of these anti-human CD3 mAbs in the murine system, an Fc-modified anti-mouse CD3 antibody (N297A) was generated. N297A exhibited similar biological effects as Fc-modified anti-human CD3 antibodies including rapid, reversible reduction in peripheral leukocyte numbers, differential modulation of activated versus resting T cells, and reduced levels of induced cytokine release compared to the non-Fc-modified parent antibody. In an in vivo model of colitis induced by adoptive transfer of IL-10-deficient cells, administration of N297A significantly reduced body weight loss. As N297A shared many functional characteristics of non-FcR binding anti-human CD3 mAbs both in vitro and in vivo, it provides a means to model the mechanisms of action of Fc-modified anti-human CD3 antibodies in mouse.
几种低或非FcR结合的抗人CD3单克隆抗体已在用于自身免疫性疾病治疗的研究中。为了在小鼠系统中模拟这些抗人CD3单克隆抗体的作用机制，制备了一种Fc修饰的抗小鼠CD3抗体（N297A）。与未修饰Fc的亲本抗体相比，N297A表现出与Fc修饰的抗人CD3抗体相似的生物学效应，包括外周白细胞数量快速、可逆性减少，对活化T细胞与静息T细胞的差异调节，以及诱导细胞因子释放水平降低。在通过IL-10缺陷细胞过继转移诱导的结肠炎体内模型中，给予N297A可显著减轻体重减轻。由于N297A在体外和体内均具有非FcR结合抗人CD3单克隆抗体的许多功能特性，它为在小鼠中模拟Fc修饰的抗人CD3抗体的作用机制提供了一种手段。
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