Chemically generated IgG2 bispecific antibodies through disulfide bridging
Chemically generated IgG2 bispecific antibodies through disulfide bridging
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DOI：
10.1016/j.bmcl.2017.07.021
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发表时间：
2017-08-15
影响因子：
2.7
通讯作者：
Kaufmann, Gunnar F.
中科院分区：
文献类型：
--
作者：
Patterson, James T.;Gros, Edwige;Kaufmann, Gunnar F.
双特异性抗体（BsAb）被设计为同时接合两种抗原，从而有效地扩展基于抗体的治疗剂靶向相同细胞内的多个途径、接合两种单独的可溶性抗原、结合具有不同互补位的相同抗原或交联两种不同细胞类型的能力。已经出现了许多重组BsAb形式，然而，此类构建体的表达和纯化通常具有挑战性。为此，我们开发了一种使用天然IgG 2结构产生BsAb的化学策略。全长抗体可以通过二硫键桥连与带有正交基团的接头缀合以产生BsAb。我们报告说，通过这种方法成功地产生了α HER 2/EGFR BsAb，并保留了结合两种抗原的能力，而没有显着的效力损失。(C)2017爱思唯尔有限公司版权所有
Bispecific antibodies (BsAbs) are designed to engage two antigens simultaneously, thus, effectively expanding the ability of antibody-based therapeutics to target multiple pathways within the same cell, engage two separate soluble antigens, bind the same antigen with distinct paratopes, or crosslink two different cell types. Many recombinant BsAb formats have emerged, however, expression and purification of such constructs can often be challenging. To this end, we have developed a chemical strategy for generating BsAbs using native IgG2 architecture. Full-length antibodies can be conjugated via disulfide bridging with linkers bearing orthogonal groups to produce BsAbs. We report that an alpha HER2/EGFR BsAb was successfully generated by this approach and retained the ability to bind both antigens with no significant loss of potency. (C) 2017 Elsevier Ltd. All rights reserved.