Engineering of therapeutic antibodies to minimize immunogenicity and optimize function

被引:151
作者
Presta, Leonard G. [1 ]
机构
[1] Schering Plough Biopharma, Dept Prot Engn, Palo Alto, CA 94304 USA
关键词
Fc receptor; effector function; humanization; FcRn;
D O I
10.1016/j.addr.2006.01.026
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
One of the first difficulties in developing monoclonal antibody therapeutics was the recognition that human anti-mouse antibody (HAMA) response limited the administration of murine antibodies. Creative science has lead to a number of ways to counter the immunogenicity of non-human antibodies, primarily through chimeric, humanized, de-immunized, and most recently, human-sequence therapeutic antibodies. Once therapeutic antibodies of low or no immunogenicity were available, the creativity then turned to engineering both the antigen-binding domains (e.g., affinity maturation, stability) and altering the effector functions (e.g. antibody-dependent cellular cytotoxicity, complement-dependent cellular cytotoxicity, and clearance rate). (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:640 / 656
页数:17
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