痛苦
表位
癌症研究
同型
免疫球蛋白类转换
敌手
CD40
兴奋剂
B细胞
药理学
生物
化学
细胞毒性T细胞
免疫学
受体
抗体
单克隆抗体
体外
生物化学
政治学
法学
政治
作者
Xiaojie Yu,H. T. Claude Chan,Hayden Fisher,Christine A. Penfold,Jinny Kim,Tatyana Inzhelevskaya,C. Ian Mockridge,Ruth R. French,Patrick J. Duriez,Leon Douglas,Vikki English,J. Sjef Verbeek,Ann L. White,Ivo Tews,Martin J. Glennie,Mark S. Cragg
出处
期刊:Cancer Cell
[Elsevier]
日期:2020-06-01
卷期号:37 (6): 850-866.e7
被引量:49
标识
DOI:10.1016/j.ccell.2020.04.013
摘要
Anti-CD40 monoclonal antibodies (mAbs) comprise agonists and antagonists, which display promising therapeutic activities in cancer and autoimmunity, respectively. We previously showed that epitope and isotype interact to deliver optimal agonistic anti-CD40 mAbs. The impact of Fc engineering on antagonists, however, remains largely unexplored. Here, we show that clinically relevant antagonists used for treating autoimmune conditions can be converted into potent FcγR-independent agonists with remarkable antitumor activity by isotype switching to hIgG2. One antagonist is converted to a super-agonist with greater potency than previously reported highly agonistic anti-CD40 mAbs. Such conversion is dependent on the unique disulfide bonding properties of the hIgG2 hinge. This investigation highlights the transformative capacity of the hIgG2 isotype for converting antagonists to agonists to treat cancer.
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