Antibody engineering for increased potency, breadth and half-life
Purpose of review: This review highlights recent developments in HIV-1 antibody engineering and discusses the effects of increased polyreactivity on serum half-lives of engineered antibodies. Recent findings: 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. Summary: 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.
© 2015 Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Post Author Corrections: March 10, 2015. We thank Sonal N. Patel for help with figure preparation. This work was supported by a Collaboration for AIDS Vaccine Discovery (CAVD) grant from the Bill and Melinda Gates Foundation (Grant ID: 1040753 to P.J.B.), National Institutes of Health grant HIVRAD P01 AI100148 (P.J.B.) and award number DP10D006961 (to P.J.B.), the American Cancer Society (Grant PF-13-076-01-MPCto L.S.), California HIV/AIDS Research Program (CHRP grant F12-CT-214 to S.A.S.).