Recombinant antibodies are key components for research, diagnostics, and biotherapeutics and can be engineered to perform specific functions or applications (e.g. isotype switching, affinity improvement). These features are of particular importance with the advent of AI-enable antibody generation and library screening approaches, which can create thousands of new antibody variants that may offer improved performance. Dr. Matt Heidtman demonstrates a workflow to express and purify ~100 recombinant antibodies in one run. He addresses the challenges that arise with large scale antibody screening campaigns, including the production of recombinant antibodies at small-scale in sufficient throughput, and the identification of robust analytical methods to identify candidates with optimal manufacturability.
Once a candidate has been selected, the development of stable, highly productive cell lines is a critical step in therapeutic antibody production. Engineering cell lines is commonly performed by random integration, resulting in a heterogeneous pool from which cells must be single cell cloned, expanded, and screened to identify high titer stable clones. This process is time and labor intensive, often requiring hundreds of clones to be screened to develop optimal cell lines. Dr. Jessica Fiege describes the process of developing CHO-K1 cell lines using the TcBuster system, which yields a 5-fold higher antibody titer than the random integration pool. TcBuster is a DNA transposon-based cell editing system that allows for stable gene transfer into virtually any cell type and quickly generates a greater number of cell clones producing high antibodies titers than random integration alone.
For antibodies produced by either high throughput methods or via stable cell line platforms, early biophysical characterization is critical to identify the most promising lead molecules. Traditional methods such as SDS-PAGE and ion exchange chromatography (IEX) can be time consuming and may require further processing steps. Dr. Srinivasa Rao illustrates two fast, simple analytical methods using the Maurice System to determine size and purity (CE-SDS) as well as charge heterogeneity (icIEF) profiles for both unpurified and purified antibodies. This analysis identifies critical quality attributes (CQAs) that can be used to select lead candidates with robust developability profiles.
In this webinar, you will learn about:
- Addressing the challenges that arise with large scale antibody screening campaigns
- Utilizing the TcBuster system to generate a greater number of cell clones with higher antibodies titers compared to random integration
- Improving the speed and accuracy of protein size analysis using CE-SDS vs SDS-PAGE
- Obtaining high resolution charge heterogeneity data using icIEF vs IEX
