High-Throughput Monoclonal Antibody Discovery from Phage Libraries: Challenging the Current Preclinical Pipeline to Keep the Pace with the Increasing mAb Demand

SIMPLE SUMMARY: Monoclonal antibodies are increasingly used for a broad range of diseases. Rising demand must face with time time-consuming and laborious processes to isolate novel monoclonal antibodies. Next-generation sequencing coupled to phage display provides timely and sustainable high throughput selection strategy to rapidly access novel target. Here, we describe the current NGS-guided strategies to identify potential binders from enriched sub-libraires by applying a user-friendly informatic pipeline to identify and discard false positive clones. Rescue step and strategies to boost mAb yield are also discussed to improve the limiting selection and screening steps. ABSTRACT: Monoclonal antibodies are among the most powerful therapeutics in modern medicine. Since the approval of the first therapeutic antibody in 1986, monoclonal antibodies keep holding great expectations for application in a range of clinical indications, highlighting the need to provide timely and sustainable access to powerful screening options. However, their application in the past has been limited by time-consuming and expensive steps of discovery and production. The screening of antibody repertoires is a laborious step; however, the implementation of next-generation sequencing-guided screening of single-chain antibody fragments has now largely overcome this issue. This review provides a detailed overview of the current strategies for the identification of monoclonal antibodies from phage display-based libraries. We also discuss the challenges and the possible solutions to improve the limiting selection and screening steps, in order to keep pace with the increasing demand for monoclonal antibodies.