Application of antibody engineering in the development of next generation antibody-based therapeutics

Abstract

The evolution of therapeutic antibodies has encompassed multiple engineering efforts in the hope of improving the efficacy, safety, and duration of effects of antibody-based drugs. Advances in protein engineering technologies afforded investigators the ability to overcome problems associated with introducing foreign antibodies into humans. These efforts included antibody chimerization, humanization, and the more recent development of human antibodies, all of which reduced anti-drug immune responses. Additional efforts have engineered antibody variable regions that encode multiple specificities into a single molecular entity. Apart from optimizing antigen-binding capabilities and reducing immunogenicity, many advances have been made that modulate an antibody's ability to interact with cells and serum components of the immune system. Manipulation of antibody glycosylation or the amino acid sequence has had a significant impact on recruitment of the Fc-dependent effector functions. This chapter presents an overview of V region and Fc modifications and focuses on advances in engineering to tailor an antibody's function relative to the intended therapeutic need.