title: Antibody engineering for increased potency, breadth and half-life.
abstract: OBJECTIVE
  This review highlights recent developments in HIV-1 antibody engineering and discusses the effects of increased polyreactivity on serum half-lives of engineered antibodies.
  
  
  RESULTS
  Recent studies have uncovered a wealth of information about the relationship between the sequences and efficacies of anti-HIV-1 antibodies through a combination of bioinformatics, structural characterization and in vivo studies. This knowledge has stimulated efforts to enhance antibody breadth and potency for therapeutic use. Although some engineered antibodies have shown increased polyreactivity and short half-lives, promising efforts are circumventing these problems.
  
  
  CONCLUSIONS
  Antibodies are desirable as therapeutics due to their ability to recognize targets with both specificity and high affinity. Furthermore, the ability of antibodies to stimulate Fc-mediated effector functions can increase their utility. Thus, mAbs have become central to strategies for the treatment of various diseases. Using both targeted and library-based approaches, antibodies can be engineered to improve their therapeutic properties. This article will discuss recent antibody engineering efforts to improve the breadth and potency of anti-HIV-1 antibodies. The polyreactivity of engineered HIV-1 bNAbs and the effect on serum half-life will be explored along with strategies to overcome problems introduced by engineering antibodies. Finally, advances in creating bispecific anti-HIV-1 reagents are discussed.
authors.affiliation: aDivision of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA bHoward Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Sievers
authors.forename: Louise
authors.initials: L
authors.lastname: Scharf
authors.forename: Anthony P
authors.initials: AP
authors.lastname: West
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific; D001665:Binding Sites; D015483:HIV Antibodies; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015202:Protein Engineering / Q000379:methods*
chemical_list: D018033:Antibodies, Bispecific; D015483:HIV Antibodies