Construction of reshaped human antibodies with HIV-neutralizing activity.
Construction of reshaped human antibodies with HIV-neutralizing activity.
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构建具有 HIV 中和活性的重塑人类抗体。
DOI：
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发表时间：
1991
期刊：
影响因子：
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通讯作者：
M. Bendig
中科院分区：
文献类型：
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作者：
H. Maeda;S. Matsushita;Y. Eda;K. Kimachi;S. Tokiyoshi;M. Bendig
小鼠单克隆抗体（mAb）0.5 β与人类免疫缺陷病毒（HIV）的包膜蛋白gp120结合，并在体外中和HIV感染。因此，小鼠mAb 0.5 β具有作为预防和治疗获得性免疫缺陷综合征（AIDS）的治疗剂的潜力。由于小鼠mAb在人类中具有高度免疫原性，因此正在努力使考虑用于人类的小鼠mAb人源化。本报告描述了重塑人0.5 β抗体的设计、构建和表达。在这些抗体中，整个恒定（C）区源自人序列。可变（V）区来源于人框架区（FR）和小鼠0.5 β互补决定区（CDR）。制备并测试了一个版本的重塑人0.5 β轻链（L）和六个版本的重塑人0.5 β重链（H）。在cos细胞中瞬时表达后，所有的构建体都能够产生类人抗体。当与L链结构（RL）共表达时，三种H链结构（RHc、RHe和RHf）产生能够结合小鼠0.5 β mAb识别的gp120上的表位的重塑的人抗体。重塑的人0.5 β抗体的最佳形式（RL + RHe）具有在小鼠或嵌合0.5 β抗体的两倍内的结合亲和力和中和活性。
Mouse monoclonal antibody (mAb) 0.5 beta binds to the envelope protein gp120 of human immunodeficiency virus (HIV) and neutralizes infection by HIV in vitro. Mouse mAb 0.5 beta, therefore, has potential as a therapeutic agent for the prevention and treatment of acquired immunodeficiency syndrome (AIDS). Since mouse mAbs are highly immunogenic in humans, efforts are being made to humanize mouse mAbs that are being considered for use in humans. This report describes the design, construction, and expression of reshaped human 0.5 beta antibodies. In these antibodies, the entire constant (C) regions were derived from human sequences. The variable (V) regions were derived from human framework regions (FRs) and mouse 0.5 beta complementarity determining regions (CDRs). One version of reshaped human 0.5 beta light (L) chain and six versions of reshaped human 0.5 beta heavy (H) chain were made and tested. Following transient expression in cos cells, all of the constructions were capable of producing humanlike antibody. Three of the H chain constructions (RHc, RHe, and RHf), when co-expressed with the L chain construction (RL), produced reshaped human antibody capable of binding to the epitope on gp120 recognized by mouse 0.5 beta mAb. The best version (RL + RHe) of reshaped human 0.5 beta antibody had both binding affinity and neutralizing activity that were within twofold that of the mouse or chimeric 0.5 beta antibody.