Recent Immunoglobulin G1 Engineering Strategies to Modulate Immune Effector Functions for Therapeutics

IgG is the most common scaffold used for antibody-based therapeutics. Utilization of the ever-expanding knowledge base of the IgG scaffold provides a wealth of design options for therapeutic development. These therapeutics apply varied engineering strategies in various combinations utilizing three key IgG features: the crystallizable fragment (Fc), antigen-binding fragment (Fab), and the conserved N-glycans. Designs may be as simple as amino acid variants to modulate effector function or as complex as large designs incorporating additional Fab, Fc, and non-IgG domain fusions to modulate effector molecule recognition, valency, and antigen specificity. The engineering strategies and basic knowledge supporting these developments have been the subject of rapid expansion. Here we review multiple approaches and advances with a focus on the last five years.