Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties
Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties
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DOI：
10.4161/mabs.22771
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发表时间：
2013-01-01
期刊：
影响因子：
5.3
通讯作者：
Niederfellner, Gerhard
中科院分区：
文献类型：
--
作者：
Klein, Christian;Lammens, Alfred;Niederfellner, Gerhard
几种新的抗cd20单克隆抗体目前正在开发中，目的是改善B细胞恶性肿瘤的治疗。诱变和表位定位研究揭示了这些抗体识别的CD20表位之间的差异。最近，x射线晶体学研究证实，I型CD20抗体利妥昔单抗和II型CD20抗体obinutuzumab （GA101）在与CD20的相互作用方面存在根本差异，尽管它们在CD20上识别出部分重叠的表位。I型CD20抗体利妥昔单抗和ofatumumab已知与不同的表位结合。这些差异表明，这些抗体的生物学特性不仅取决于它们的核心表位序列，还取决于其他因素，如肘部铰链角、结合抗体的取向和抗体Fc区介导的差异效应。综上所述，这些因素可能解释了抗cd20抗体临床前特性和临床疗效的差异。
Several novel anti-CD20 monoclonal antibodies are currently in development with the aim of improving the treatment of B cell malignancies. Mutagenesis and epitope mapping studies have revealed differences between the CD20 epitopes recognized by these antibodies. Recently, X-ray crystallography studies confirmed that the Type I CD20 antibody rituximab and the Type II CD20 antibody obinutuzumab (GA101) differ fundamentally in their interaction with CD20 despite recognizing a partially overlapping epitope on CD20. The Type I CD20 antibodies rituximab and ofatumumab are known to bind to different epitopes. The differences suggest that the biological properties of these antibodies are not solely determined by their core epitope sequences, but also depend on other factors, such as the elbow hinge angle, the orientation of the bound antibody and differential effects mediated by the Fc region of the antibody. Taken together, these factors may explain differences in the preclinical properties and clinical efficacy of anti-CD20 antibodies.