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High-throughput functional screening for next-generation cancer immunotherapy using droplet-based microfluidics

Currently, high-throughput approaches are lacking in the isolation of antibodies with functional readouts beyond simple binding. This situation has impeded the next generation of cancer immunotherapeutics, such as bispecific T cell engager (BiTE) antibodies or agonist antibodies against costimulator...

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Detalles Bibliográficos
Autores principales: 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, Tian, Yujie, Cao, Youjia, Li, Fubin, Schweizer, Liang, Zhang, Hongkai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195480/
https://www.ncbi.nlm.nih.gov/pubmed/34117053
http://dx.doi.org/10.1126/sciadv.abe3839
Descripción
Sumario:Currently, high-throughput approaches are lacking in the isolation of antibodies with functional readouts beyond simple binding. This situation has impeded the next generation of cancer immunotherapeutics, such as bispecific T cell engager (BiTE) antibodies or agonist antibodies against costimulatory receptors, from reaching their full potential. Here, we developed a highly efficient droplet-based microfluidic platform combining a lentivirus transduction system that enables functional screening of millions of antibodies to identify potential hits with desired functionalities. To showcase the capacity of this system, functional antibodies for CD40 agonism with low frequency (<0.02%) were identified with two rounds of screening. Furthermore, the versatility of the system was demonstrated by combining an anti-Her2 × anti-CD3 BiTE antibody library with functional screening, which enabled efficient identification of active anti-Her2 × anti-CD3 BiTE antibodies. The platform could revolutionize next-generation cancer immunotherapy drug development and advance medical research.