The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies
The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies
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DOI：
10.1074/jbc.275.18.13668
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发表时间：
2000-05-05
影响因子：
4.8
通讯作者：
Barbas, CF
中科院分区：
文献类型：
--
作者：
Rader, C;Ritter, G;Barbas, CF
以多克隆抗体形式存在的兔抗体库已经在诊断应用中使用了几十年，将是产生治疗性人抗体的有吸引力的来源。然而，兔抗体的人源化尚未报道。本研究利用噬菌体展示技术，从人结肠癌免疫治疗的靶抗原A33免疫的兔中筛选抗体并进行人源化。我们首先选择了与人A33抗原的细胞表面表位结合的兔抗体，亲和力在1 nM范围内。对于兔抗体人源化，我们随后使用了将互补决定区的移植与框架微调相结合的选择策略。发现所得人源化抗体保留对人A33抗原的高特异性和亲和力。
The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic applications for decades, would be an attractive source for the generation of therapeutic human antibodies. The humanization of rabbit antibodies, however, has not been reported. Here we use phage display technology to select and humanize antibodies from rabbits that were immunized with human A33 antigen which is a target antigen for the immunotherapy of colon cancer. We first selected rabbit antibodies that bind to a cell surface epitope of human A33 antigen with an affinity in the 1 nM range. For rabbit antibody humanization, we then used a selection strategy that combines grafting of the complementarity determining regions with framework fine tuning. The resulting humanized antibodies were found to retain both high specificity and affinity for human A33 antigen.