Multi-pass trans-membrane and multimeric membrane proteins are targets for the development of therapeutic monoclonal antibodies. However, they present challenges for expression, antibody generation and screening. Success requires a multi-faceted approach with the following key elements:

• A system for stable expression of the membrane target protein, at high levels, in a variety of cell lines.
• The ability to generate immunogens that present a native, bio-active state with appropriate quaternary structure. Potential immunogens include peptides, soluble protein domains, nanodiscs, proteoliposomes, intact cells, and DNA vectors.
• Effective immunization protocols tailored to the immunogens.
• A robust platform for capturing the antibody response.
• A high-throughput screening platform for detecting antibodies on target protein-expressing cells

Summary

We present an integrated platform for antibody discovery to membrane protein targets. Key elements for success include the ability to generate and use a variety of immunogens and to screen antibodies versus cells bearing the target antigen. Ultimately, success depends upon appropriate design and implementation of the above elements, with an overall strategy based upon the nature of each target.

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We invite you to download our poster that details this research study, including our antibody discovery strategy as well as the Spike protein reagents, screening assay formats, and more that we utilized.

Authors

shua K. Lowitz, Glen Lin, Leonel Santibanez-Vargas, Jennifer Somera, Billy Nguyen, and John S. Kenney Antibody Solutions, Sunnyvale, CA, USA, Palo Alto, CA USA

Presented at Antibody Engineering & Therapeutics, December 11-15, 2016