Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Darmstadt, Germany.
Institute for Molecular Biotechnology, University of Bodenkultur, Vienna, Austria.
MAbs. 2021 Jan-Dec;13(1):1978130. doi: 10.1080/19420862.2021.1978130.
Recent years have seen unparalleled development of microfluidic applications for antibody discovery in both academic and pharmaceutical research. Microfluidics can support native chain-paired library generation as well as direct screening of antibody secreting cells obtained by rodent immunization or from the human peripheral blood. While broad diversities of neutralizing antibodies against infectious diseases such as HIV, Ebola, or COVID-19 have been identified from convalescent individuals, microfluidics can expedite therapeutic antibody discovery for cancer or immunological disease indications. In this study, a commercially available microfluidic device, Cyto-Mine, was used for the rapid identification of natively paired antibodies from rodents or human donors screened for specific binding to recombinant antigens, for direct screening with cells expressing the target of interest, and, to our knowledge for the first time, for direct broad functional IgG antibody screening in droplets. The process time from cell preparation to confirmed recombinant antibodies was four weeks. Application of this or similar microfluidic devices and methodologies can accelerate and enhance pharmaceutical antibody hit discovery.
近年来，微流控技术在学术和药物研究领域的抗体发现中得到了前所未有的发展。微流控技术可以支持天然配对文库的生成，以及对通过啮齿动物免疫或从人外周血获得的分泌抗体的细胞进行直接筛选。虽然已经从康复个体中鉴定出针对艾滋病毒、埃博拉或 COVID-19 等传染病的广泛中和抗体，但微流控技术可以加速针对癌症或免疫疾病适应症的治疗性抗体的发现。在这项研究中，使用了一种商业上可用的微流控设备 Cyto-Mine，用于从筛选出与重组抗原特异性结合的啮齿动物或人类供体中快速鉴定天然配对的抗体，用于直接与表达感兴趣靶标的细胞进行筛选，并且据我们所知，这是首次在液滴中直接进行广泛的功能性 IgG 抗体筛选。从细胞制备到确认重组抗体的过程时间为四周。应用这种或类似的微流控设备和方法可以加速和增强药物抗体发现的命中率。
