Efficient development of a stable cell pool for antibody production using a single plasmid

Area of Science:

• Biopharmaceutical Development
• Protein Expression Systems

Background:

• Therapeutic antibodies represent a rapidly expanding class of biopharmaceuticals.
• Efficient production of substantial antibody quantities is essential for drug candidate evaluation.
• Current methods for stable cell pool development are often labor-intensive due to low frequencies of high-producing clones.

Purpose of the Study:

• To establish an efficient strategy for constructing stable antibody-expressing cell pools.
• To identify optimal expression vectors and screening parameters for antibody production.
• To reduce the labor and cost associated with developing high-yield antibody-producing cell lines.

Main Methods:

• Optimization of expression vectors and screening parameters for stable cell pool construction.
• Development of a streamlined screening strategy to identify high-producing clones.
• Assessment of expression titers and product purity using size-exclusion chromatography.

Main Results:

• The optimized strategy resulted in a 10-fold improvement in antibody expression titers.
• A higher proportion of cell pools achieved >95% purity of the main product peak.
• High-producing clones were identified by screening only five 96-well plates.

Conclusions:

• The developed strategy significantly enhances the efficiency of stable antibody-expressing cell pool construction.
• This approach offers substantial cost and labor savings for producing two-subunit proteins like antibodies.
• The optimized platform facilitates reduced clone-screening efforts, particularly beneficial during Clinical Lead Selection.