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

Area of Science:

• Biotechnology
• Immunology
• Microfluidics

Background:

• High-throughput antibody isolation methods often lack functional readouts beyond simple binding.
• This limitation hinders the development of advanced cancer immunotherapeutics like bispecific T cell engagers (BiTEs) and costimulatory receptor agonists.

Purpose of the Study:

• To develop a microfluidic platform for high-throughput functional screening of antibodies.
• To enable the isolation of antibodies with desired functionalities for cancer immunotherapy.

Main Methods:

• A droplet-based microfluidic platform was combined with a lentivirus transduction system.
• Millions of antibodies were functionally screened to identify hits with specific therapeutic functions.

Main Results:

• Functional CD40 agonistic antibodies, present at a low frequency (<0.02%), were identified in two screening rounds.
• The platform successfully identified active anti-Her2 × anti-CD3 BiTE antibodies from a diverse library.

Conclusions:

• The developed platform significantly enhances the discovery of functional antibodies for next-generation cancer immunotherapies.
• This technology has the potential to revolutionize cancer drug development and advance medical research.