Antibody Research

Multipass transmembrane and multimeric membrane proteins are targets for the development of therapeutic monoclonal antibodies, but they present challenges for antibody generation. Membrane proteins represent ~25% of the entire genome and the majority of those are multi-pass, complex proteins that are challenging to express in a native, bio-active state with appropriate quaternary structure.

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

Preclinical and clinical pharmacokinetic (PK) studies require highly specific and high affinity immunoassays to evaluate the safety and efficacy of therapeutic monoclonal antibodies (MAbs). In addition to the requirement that immunoassays specifically detect therapeutic MAbs without interference from host serum proteins, it is increasingly critical to develop reagents that allow differentiation between Free (Unbound) and Total (Bound + Unbound) drug. These reagents help to more fully characterize in vivo drug:target interaction and illustrate the full pharmacologic effect of therapeutic MAbs.

Multi-pass transmembrane and multi-meric membrane proteins are targets for the development of therapeutic monoclonal antibodies, but are often challenging or impossible to express in a native, bio-active state with appropriate quaternary structure. Immunization with surrogate forms of the target including peptides, soluble protein domains, proteo-liposomes, or intact cells are not always successful in producing antibodies that are capable of binding to native state proteins.