双特异性抗体
抗体
单克隆抗体
化学
抗体反应
计算生物学
蛋白质工程
生物
噬菌体展示
微生物学
免疫学
癌症研究
生物化学
酶
作者
Christoph Spiess,Mark Merchant,Arthur Huang,Zhong Zheng,Nai‐Ying Yang,Jing Peng,Diego Ellerman,Whitney Shatz,Dorothea Reilly,Daniel G. Yansura,Justin M. Scheer
摘要
By enabling the simultaneous engagement of two distinct targets, bispecific antibodies broaden the potential utility of antibody-based therapies. However, bispecific-antibody design and production remain challenging, owing to the need to incorporate two distinct heavy and light chain pairs while maintaining natural nonimmunogenic antibody architecture. Here we present a bispecific-antibody production strategy that relies on co-culture of two bacterial strains, each expressing a half-antibody. Using this approach, we produce 28 unique bispecific antibodies. A bispecific antibody against the receptor tyrosine kinases MET and EGFR binds both targets monovalently, inhibits their signaling, and suppresses MET and EGFR-driven cell and tumor growth. Our strategy allows rapid generation of bispecific antibodies from any two existing antibodies and yields milligram to gram quantities of bispecific antibodies sufficient for a wide range of discovery and preclinical applications.
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