The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.
The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.
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DOI：
10.3390/ijms22168947
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发表时间：
2021-08-19
影响因子：
5.6
通讯作者：
Anzaghe M
中科院分区：
文献类型：
--
作者：
Gogesch P;Dudek S;van Zandbergen G;Waibler Z;Anzaghe M
自1986年第一株单抗问世以来，人们为保证治疗性单抗的安全性和有效性做出了巨大的努力。截至2021年7月，欧洲市场批准了118种单抗用于广泛的临床适应症。为了确保临床疗效和安全性，(临床前)实验方法评估各自的作用模式(MOA)。除了包括结合亲和力和亲和力在内的抗原特异性，MOA还包括Fc介导的效应功能，如抗体依赖的细胞毒性(ADCC)和密切相关的抗体依赖的细胞吞噬作用(ADCP)。为此，已经建立了各种基于细胞的分析方法，用不同的效应器/靶细胞组合和几种读数来研究治疗性单抗的效应功能，包括Fcγ受体(FcγR)介导的裂解、荧光或发光。优化的FcγR介导的效应器功能与临床安全性和有效性有关的修饰策略，如点突变、糖基化模式改变、不同Fc亚类的组合(交叉亚型)和Fc-mAb的截短。这些策略为下一代治疗性单抗开辟了领域。综上所述，考虑FcγR介导的效应器功能对于治疗性单抗的疗效是非常重要的。
Since the approval of the first monoclonal antibody (mAb) in 1986, a huge effort has been made to guarantee safety and efficacy of therapeutic mAbs. As of July 2021, 118 mAbs are approved for the European market for a broad range of clinical indications. In order to ensure clinical efficacy and safety aspects, (pre-)clinical experimental approaches evaluate the respective modes of action (MoA). In addition to antigen-specificity including binding affinity and -avidity, MoA comprise Fc-mediated effector functions such as antibody dependent cellular cytotoxicity (ADCC) and the closely related antibody dependent cellular phagocytosis (ADCP). For this reason, a variety of cell-based assays have been established investigating effector functions of therapeutic mAbs with different effector/target-cell combinations and several readouts including Fcγ receptor (FcγR)-mediated lysis, fluorescence, or luminescence. Optimized FcγR-mediated effector functions regarding clinical safety and efficacy are addressed with modification strategies such as point mutations, altered glycosylation patterns, combination of different Fc subclasses (cross isotypes), and Fc-truncation of the mAb. These strategies opened the field for a next generation of therapeutic mAbs. In conclusion, it is of major importance to consider FcγR-mediated effector functions for the efficacy of therapeutic mAbs.
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影响因子：
2.2
作者：
Bussiere, Jeanine L.;Martin, Pauline;Horvath, Christopher
通讯作者：
Horvath, Christopher
DOI：
10.1084/jem.173.6.1483
发表时间：
1991-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Canfield SM;Morrison SL
通讯作者：
Morrison SL
影响因子：
3
作者：
Ahmed, Alysia A.;Keremane, Sravya R.;Bjorkman, Pamela J.
通讯作者：
Bjorkman, Pamela J.
DOI：
10.1074/jbc.rev120.013168
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Barb AW
通讯作者：
Barb AW
影响因子：
5.4
作者：
BOLT, S;ROUTLEDGE, E;WALDMANN, H
通讯作者：
WALDMANN, H