竞争行为
抑制性突触后电位
佐剂
抗体
CD40
受体
双特异性抗体
化学
免疫学
生物
医学
单克隆抗体
神经科学
生物化学
体外
细胞毒性T细胞
精神科
侵略
作者
Fubin Li,Jeffrey V. Ravetch
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2011-08-18
卷期号:333 (6045): 1030-1034
被引量:314
标识
DOI:10.1126/science.1206954
摘要
CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, is expressed on antigen-presenting cells (APCs) and is essential for immune activation. Although agonistic CD40 antibodies have been developed for immunotherapy, their clinical efficacy has been limited. We have found that coengagement of the Fc domain of agonistic CD40 monoclonal antibodies (mAbs) with the inhibitory Fcγ receptor FcγRIIB is required for immune activation. Direct comparison of mAbs to CD40 enhanced for activating FcγR binding, hence capable of cytotoxicity, or for inhibitory FcγRIIB binding, revealed that enhancing FcγRIIB binding conferred immunostimulatory activity and considerably greater anti-tumor responses. This unexpected requirement for FcγRIIB in enhancing CD40-mediated immune activation has direct implications for the design of agonistic antibodies to TNFR as therapeutics.
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