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

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A new microfluidic platform enables high-throughput functional screening of antibodies for cancer immunotherapy. This technology accelerates the discovery of potent bispecific T cell engager (BiTE) antibodies and costimulatory receptor agonists.

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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.