Mapping effector functions of a monoclonal antibody to GD3 by characterization of a mouse-human chimeric antibody.
Mapping effector functions of a monoclonal antibody to GD3 by characterization of a mouse-human chimeric antibody.
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通过表征小鼠-人嵌合抗体来绘制 GD3 单克隆抗体的效应子功能。
DOI：
10.1007/bf01533387
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Reilly,RM
中科院分区：
文献类型：
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作者：
Chapman,PB;Gillies,SD;Houghton,AN;Reilly,RM
R24是一种抗GD 3神经节苷脂的小鼠单克隆抗体，具有广泛的体外效应功能。它还具有与自身结合的能力，推测是通过同源性Fab-Fab相互作用，这已被提出有助于其对GD 3的高相对亲合力及其效应子功能活性。尚不清楚这些特征中的哪一个是在用R24治疗的黑素瘤患者中观察到的抗肿瘤作用所必需的。已经构建了小鼠-人嵌合R24（chR 24）分子，其中保留了GD 3结合位点。嵌合体R24与GD 3的结合水平低于小鼠R24，这表明两种mAb的GD 3结合位点之间可能存在一些差异，或者Fc决定簇可有助于R24对GD 3的亲合力。ChR 24保留了嗜同性结合的性质，正式证明R24的嗜同性结合涉及可变结构域之间的相互作用。R24和chR 24都固定人补体并介导抗体依赖性细胞毒性，尽管chR 24在后者中的效率略低。与R24不同，chR 24不能抑制黑色素瘤细胞附着在塑料表面，也不能激活人类T淋巴细胞。我们假设chR 24不以足够高的亲合力与GD 3结合以介导这些效应子功能。
R24, a mouse monoclonal antibody against GD3 ganglioside, exhibits a wide range of in vitro effector functions. It also has the ability to bind to itself, presumably through homophilic Fab-Fab interactions, which have been proposed to contribute to its high relative avidity for GD3 and to its effector function activity. It is not known which of these characteristics is necessary for the antitumor effects observed in melanoma patients treated with R24. A mouse-human chimeric R24 (chR24) molecule has been constructed in which the GD3-binding site is preserved. Chimeric R24 demonstrates a lower level of binding to GD3 than does mouse R24 suggesting that there may be some differences between the GD3-binding sites of the two mAb or that Fc determinants can contribute to R24 avidity for GD3. The property of homophilic binding is retained by chR24, demonstrating formally that homophilic binding of R24 involves interactions between variable domains. Both R24 and chR24 fix human complement and mediate antibody-dependent cellular cytotoxicity although chR24 was slightly less efficient at the latter. Unlike R24, chR24 was not able to inhibit melanoma cell attachment to plastic surfaces and was not able to activate human T lymphocytes. We hypothesize that chR24 does not bind to GD3 with an avidity high enough to mediate these effector functions.