Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody
Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody
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DOI：
10.1093/protein/9.3.299
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发表时间：
1996-03-01
期刊：
影响因子：
--
通讯作者：
Winter, G
中科院分区：
文献类型：
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作者：
Holliger, P;Brissinck, J;Winter, G
通过细菌发酵产生的抗体片段缺乏天然效应子功能。然而，双特异性抗体片段可以通过结合细胞毒性细胞并重新靶向细胞毒性细胞而被赋予效应子功能，例如细胞介导的杀伤。双抗体是一类具有两个抗原结合位点的工程化抗体片段，由两条相关链组成;每条链由通过短多肽接头连接的重链和轻链可变结构域组成。与IgG或其中两个结合位点可以占据一定范围的取向和间距的其它抗体片段相反，双抗体结构更加刚性和紧凑，两个结合位点相隔65埃（小于IgG中距离的一半）。为了确定双抗体是否也可以用于细胞介导的杀伤，我们已经探索了与小鼠B细胞淋巴瘤（BCL-1）上的独特型标记和小鼠CD 3结合的双特异性双抗体的用途，双特异性双抗体活化幼稚T细胞，并且还介导细胞毒性T细胞对淋巴瘤细胞的特异性杀伤。双抗体在T细胞活化中活性较低，但在杀伤中比类似的双特异性IgG活性高10倍（w/v）。
Antibody fragments produced by bacterial fermentation lack natural effector functions, Bispecific antibody fragments, however, can be endowed with effector functions, for example cell-mediated killing, by binding to and retargeting of cytotoxic cells, Diabodies are a class of engineered antibody fragments with two antigen binding sites, consisting of two associated chains; each chain consists of heavy and light chain variable domains linked by a short polypeptide linker, In contrast to IgG, or other antibody fragments in which the two binding sites can take up a range of orientations and spacings, the diabody structure is more rigid and compact, with the two binding sites separated by 65 Angstrom (less than half the distance in IgG), To establish whether diabodies could also be used in cell-mediated killing, we have explored the use of a bispecific diabody binding to an idiotypic marker on mouse B-cell lymphoma (BCL-1) and to mouse CD3, The bispecific diabody activated naive T-cells and also mediated the specific killing of the lymphoma cells by cytotoxic T-cells, The diabody was less active in T-cell activation but 10-fold more active (w/v) in killing than an analogous bispecific IgG.