Advances in Antibody Design.
The use of monoclonal antibodies as therapeutics requires optimizing several of their key attributes. These include binding affinity and specificity, folding stability, solubility, pharmacokinetics, effector functions, and compatibility with the attachment of additional antibody domains (bispecific antibodies) and cytotoxic drugs (antibody-drug conjugates). Addressing these and other challenges requires the use of systematic design methods that complement powerful immunization and in vitro screening methods. We review advances in designing the binding loops, scaffolds, domain interfaces, constant regions, post-translational and chemical modifications, and bispecific architectures of antibodies and fragments thereof to improve their bioactivity. We also highlight unmet challenges in antibody design that must be overcome to generate potent antibody therapeutics.
Center for Biotechnology and Interdisciplinary Studies, Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180; email: tessier@rpi.edu.
Kathryn E
KE
Tiller
Center for Biotechnology and Interdisciplinary Studies, Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180; email: tessier@rpi.edu.
Peter M
PM
Tessier
D000818:Animals; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000915:Antibody Affinity; D000918:Antibody Specificity; D019020:Directed Molecular Evolution; D006801:Humans; D018796:Immunoconjugates; D008958:Models, Molecular; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D055550:Protein Stability
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates
CDR; Fab; IgG; VH; complementarity-determining region; scFv