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

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

来源:bioRxiv_logobioRxiv
英文摘要

Abstract Currently 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.

Fang Pan、Wang Shanshan、Mary Pascaline、Cao Youjia、Shen Bingqing、Zhao Yingjie、Schweizer Liang、Wang Ruikun、Wang Wei、Jin Ruina、Zhou He、Zhang Hongkai、Ma Peixiang、Huang Mengshi、Li Fubin、Wang Yuan、Li Ruonan、Li Na

HiFiBiO (Shanghai) Co. LtdHiFiBiO (Shanghai) Co. LtdHiFiBiO (Shanghai) Co. LtdCollege of Life Sciences, Nankai UniversityHiFiBiO (Shanghai) Co. LtdShanghai Institute of Immunology, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine||Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineHiFiBiO (Shanghai) Co. LtdCollege of Life Sciences, Nankai UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityState Key Laboratory of Medicinal Chemical Biology, Nankai University||College of Life Sciences, Nankai UniversityHiFiBiO (Shanghai) Co. LtdState Key Laboratory of Medicinal Chemical Biology, Nankai University||College of Life Sciences, Nankai University||Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University||Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine||Key Laboratory of Immune Microenvironment and Disease, Tianjin Medical UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityHiFiBiO (Shanghai) Co. LtdShanghai Institute of Immunology, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine||Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Medicinal Chemical Biology, Nankai University||College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Nankai University||College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Nankai University||College of Life Sciences, Nankai University

10.1101/2020.11.25.399188

医学研究方法肿瘤学生物科学研究方法、生物科学研究技术

functional screeningdroplet-based microfluidicslentivirus libraryagonist antibodybispecific T cell engager antibodyimmunotherapy

Fang Pan,Wang Shanshan,Mary Pascaline,Cao Youjia,Shen Bingqing,Zhao Yingjie,Schweizer Liang,Wang Ruikun,Wang Wei,Jin Ruina,Zhou He,Zhang Hongkai,Ma Peixiang,Huang Mengshi,Li Fubin,Wang Yuan,Li Ruonan,Li Na.High throughput functional screening for next generation cancer immunotherapy using droplet-based microfluidics[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.11.25.399188.点此复制

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