Leveraging SBDD in protein therapeutic development: antibody engineering.
Antibodies make up the largest, growing segment of protein therapeutics in the pharmaceutical and biotechnology industries. The development or engineering of therapeutic antibodies is based to a large extent on our knowledge of antibody structure and requires sophisticated methods that continue to evolve. In this chapter, after a review of what is known about the structure and functional properties of antibodies, the current, state-of-the-art antibody engineering methods are described. These methods include antibody humanization, antigen-affinity optimization, Fc engineering for modulated effector function and extended half-life, and engineering for improved stability and biophysical properties. X-ray crystallographic structures of antibody fragments and their complexes can play a critical role in guiding and, in some cases, accelerating these processes. These approaches represent guidelines for developing antibody therapeutics with the desired affinity, effector function, and biophysical properties.
Centocor R&D Inc., Radnor, PA, USA. ggillila@its.jnj.com
Gary L
GL
Gilliland
Jinquan
J
Luo
Omid
O
Vafa
Juan Carlos
JC
Almagro
D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D015202:Protein Engineering
D000906:Antibodies