Strategies for simultaneous display and secretion of antibodies in CHO

Science

Antibodies are proteins used as medicines to treat diseases such as cancer and autoimmune disorders. To make these medicines, scientists rely on living cells to produce antibodies in large amounts. However, making sure cells produce the right antibodies efficiently is challenging, especially when evaluating varying antibody designs. Our research focuses on improving how laboratory-grown cells (called CHO cells) can simultaneously produce antibodies and display them on their surface. This allows scientists to quickly identify which antibodies work best while still ensuring they can be made efficiently for real-world use.

Societal Impact

This research can significantly improve how therapeutic antibodies are developed and manufactured. By enabling faster and more reliable screening of antibody candidates directly in production-like cells, our approach can reduce development time, lower manufacturing risk, and potentially decrease overall costs associated with failed drug candidates. More broadly, this platform supports innovation in biologics development and enhance competitiveness in the biopharmaceutical sector.

Technical Summary

We developed and evaluated co-expression strategies that enable monoclonal antibodies to be both surface-displayed and secreted simultaneously in CHO cells. Different vector designs were assessed to balance heavy and light chain expression while maintaining antibody integrity and functionality. Surface-displayed antibodies allowed rapid in situ screening by flow cytometry, while secreted antibodies enabled downstream biochemical and functional characterization without reformatting.

Our findings demonstrate that optimised co-expression designs can preserve genotype–phenotype linkage and improve screening efficiency without compromising manufacturability-relevant properties. This integrated display–secretion workflow provides a scalable and industry-relevant platform for antibody discovery and engineering, reducing the disconnect between early screening systems and final production formats.

Figure 1. Vector strategies for antibody LC and HC co-expression in CHO dual display–secretion systems
Comparison of multiple promoter, IRES, and 2A-based designs for coordinated light chain (LC) and heavy chain (HC) expression. Integration into a defined genomic landing pad enables simultaneous antibody display and secretion, where balanced LC/HC expression is critical for proper assembly and functional screening.

References

Ng JPZ, Mariati M, Ong HK, Bi X, Chang M, Yang Y. Optimizing co-expression strategies for the simultaneous display and secretion of monoclonal antibodies in CHO cells. Sci Rep. 2025 Nov 27;15(1):42508. doi: 10.1038/s41598-025-26682-x. PMID: 41310350; PMCID: PMC12660842.