小鼠单克隆抗体HAb25可变区的人源化计算机辅助设计

Computer aided CDR grafted humanization design of the variable region of a hepatocellular carcinoma specific monoclonal antibody HAb25

目的：对一株肝癌特异性小鼠单克隆抗体ＨＡｂ２５可变区进行人源化设计，通过人源化降低其免疫原性。方法：进行抗体结构同源模建，以计算机分析为主要手段，结合多重序列比较，进行人源化设计。结果：预测了ＨＡｂ２５可变区的立体结构，分析了决定抗体互补决定区初始构象的可能残基，提出了ＨＡｂ２５可变区的人源化替代方案。

Objective: To propose a humanization strategy for reducing the immunogenecity of the variable region of a hepatocellular carcinoma (HCC) specific murine monoclonal antibody HAb25. Methods: Computer aided analysis based upon homology modeling in addition to multiple sequences alignment was applied in the study. Results: The 3 dimensional structure of the variable region was predicted and the critical residues for the natural conformation of complementarity determining region(CDR) were listed. Based upon these, a CDR grafted humanization strategy for HAb25 was proposed. Conclusion: On the basis of structure information, computer aided analysis is an indispensable help to the humanization design.