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

Currently, high-throughput approaches are lacking in the isolation of antibodies with functional readouts beyond simple binding. This situation has impeded the next generation of cancer immunotherapeutics, such as bispecific T cell engager (BiTE) antibodies or agonist antibodies against costimulatory receptors, from reaching their full potential. Here, we developed a highly efficient droplet-based microfluidic platform combining a lentivirus transduction system that enables functional screening of millions of antibodies to identify potential hits with desired functionalities. To showcase the capacity of this system, functional antibodies for CD40 agonism with low frequency (<0.02%) were identified with two rounds of screening. Furthermore, the versatility of the system was demonstrated by combining an anti-Her2 x anti-CD3 BiTE antibody library with functional screening, which enabled efficient identification of active anti-Her2 x anti-CD3 BiTE antibodies. The platform could revolutionize next-generation cancer immunotherapy drug development and advance medical research.

Automated summary

The lack of high-throughput approaches in isolating antibodies with functional readouts has hindered the advancement of next-generation cancer immunotherapeutics. The development of a highly efficient droplet-based microfluidic platform offers a solution for functional screening of millions of antibodies, potentially revolutionizing drug development in cancer immunotherapy.