Expert view: Multiplexed screens in biologics discovery

Posted: 7 September 2018 | | No comments yet

Biologics are the fastest growing class of therapeutics in the biopharmaceutical industry. A key driver for this growth is success with anti-cancer immunotherapeutics such as checkpoint modulation, adoptive cell therapy and bispecific T-cell engagers. While these approaches use different tactics to attack tumours, they often employ monoclonal antibodies to target specific antigens.

In this highly competitive field it is crucial to identify candidate antibodies with superior target reactivity. The first step in this process involves high‑throughput screening of antibody libraries to identify binders. High-throughput flow cytometry has enabled the incorporation of multiplexing into antibody screening assays, and has greatly enhanced the discovery of novel biologics.

The key to multiplexed screening assays is the concept of encoding, in which different fluorescent dyes are used to label multiple cell lines or beads displaying target antigens on their surface. Using this technique, scientists can evaluate large antibody libraries for binders to two or more target antigens in a single screening experiment. A key application for multiplexed encoding is the mixing of two different cell lines – one displaying a target antigen and one displaying a control antigen – in the same wells of assay plates.

Antibodies binding to target but not control antigens are easily identified, improving workflow and increasing confidence in lead candidates. Perhaps an even more striking example of multiplexed screening is encoding multiple cell lines; each displaying a target antigen from a different animal species, enabling the identification of binders with cross‑species antigen reactivity. This is invaluable when developing antibodies that bind to human target antigens but can also be used in relevant animal models of toxicity and efficacy.

Advancements in high-throughput flow cytometry are enabling antibody discovery scientists to incorporate multiplexed assays into screening campaigns. These screens are being used in programs for novel immunotherapeutics involving PD‑1/PDL‑1, chimeric antigen receptors and bispecific T-cell engagers, resulting in better and safer candidates treatments for serious diseases.