Mammalian display to secretion switchable libraries for antibody preselection and high throughput functional...

Area of Science:

• Biotechnology
• Immunology
• Drug Discovery

Background:

• Mammalian libraries and microfluidic technologies are advancing therapeutic antibody discovery.
• Mammalian libraries preserve immune repertoires and facilitate bispecific antibody screening.
• Microfluidic methods enable rapid, high-content screening of antibody candidates.

Purpose of the Study:

• To explore the synergistic potential of combining microfluidic technologies with mammalian libraries for antibody discovery.
• To develop and validate integrated workflows for identifying optimal therapeutic antibody candidates.
• To demonstrate proof-of-concept for novel antibody discovery and optimization strategies.

Main Methods:

• Utilized antibody secretion, target co-expression, and reporter cell lines for bispecific antibody selection.
• Established a functional screen for antibody internalization, comparing autocrine and co-encapsulation methods.
• Implemented cell synchronization and a display-to-secretion switchable system for pre-enrichment and manufacturability sorting.

Main Results:

• Successfully selected in-trans acting agonistic bispecific antibodies.
• Identified autocrine one-cell approaches as advantageous for internalization screens.
• Demonstrated reduced assay variability through cell synchronization.
• Developed a system for pre-enriching antibody clones with high manufacturability.

Conclusions:

• The integration of microfluidic technologies and mammalian libraries is feasible for therapeutic antibody discovery.
• The developed workflows enable simultaneous screening for functional properties and manufacturability.
• This approach provides a foundation for optimizing the identification of superior therapeutic antibody candidates.