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.
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使用基于液滴的微流控技术对下一代癌症免疫疗法进行高通量功能筛选
DOI：
10.1126/sciadv.abe3839
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发表时间：
2021-06
期刊：
影响因子：
13.6
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Wang Y;Jin R;Shen B;Li N;Zhou H;Wang W;Zhao Y;Huang M;Fang P;Wang S;Mary P;Wang R;Ma P;Li R;Tian Y;Cao Y;Li F;Schweizer L;Zhang H
微流控系统能够对癌症免疫治疗的抗体进行高通量功能筛选。目前，高通量方法在分离具有超出简单结合的功能读数的抗体中缺乏。这种情况阻碍了下一代癌症免疫治疗剂，如双特异性T细胞增殖剂（BiTE）抗体或针对共刺激受体的激动剂抗体，以达到其全部潜力。在这里，我们开发了一种高效的基于液滴的微流体平台，结合了慢病毒转导系统，能够对数百万种抗体进行功能筛选，以识别具有所需功能的潜在命中。为了展示该系统的能力，用两轮筛选鉴定具有低频率（<0.02%）的CD40激动作用的功能性抗体。此外，通过将抗Her2 ×抗CD3 BiTE抗体文库与功能筛选相结合，证明了该系统的通用性，这使得能够有效地鉴定活性抗Her2 ×抗CD3 BiTE抗体。该平台可以彻底改变下一代癌症免疫治疗药物的开发和推进医学研究。
Microfluidics system enables high-throughput functional screening of antibodies for cancer immunotherapy. 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.
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