Author:
Wang Yuan,Jin Ruina,Shen Bingqing,Li Na,Zhou He,Wang Wei,Zhao Yingjie,Huang Mengshi,Fang Pan,Wang Shanshan,Mary Pascaline,Wang Ruikun,Ma Peixiang,Li Ruonan,Cao Youjia,Li Fubin,Schweizer Liang,Zhang Hongkai
Abstract
AbstractCurrently high throughput approaches are lagged for isolation of antibodies whose function goes beyond simple binding, which have prevented the next generation cancer immunotherapeutics, such as bispecific T cell engager antibodies or agonist antibody of costimulatory receptor, from reaching their full potential. Here we developed a highly efficient droplet-based microfluidics platform combining with lentivirus transduction system that enables functional screening of millions of antibodies. To showcase the capacity of the system, functional antibodies for CD40 agonism with low frequency (<0.02%) were identified with 2 rounds of screening. To demonstrate its versatility, an anti-Her2/anti-CD3 bispecific antibody library was established using bispecific T cell Engager (BiTE) platform and functional screening enabled efficient identification of potent anti-Her2/anti-CD3 BiTE antibodies. The platform could revolutionize the next generation cancer immunotherapy drug development and research world.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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