Virtual Issue: Antibody engineering

Virtual Issue: Antibody engineering

Antibodies are a favorite tool for genetic engineers. They have also become profoundly important therapeutic agents, applied to diseases ranging from autoimmunity to cancer. Many were originally monoclonal mouse IgG antibodies recognizing human cell surface molecules, for example CD20 targeted in the treatment of B-cell lymphomas and autoimmune diseases such as Multiple Sclerosis. Others recognize soluble molecules, for example cytokines such as TNFα. Early engineering focused on replacing mouse sequences with human ones to minimize immune responses. Since then, numerous other modifications have been made, and imagination now appears to be the only limitation to progress in this incredibly innovative field. This virtual issue celebrates these innovations, covering research from the past four years. First, the collection captures approaches to enhance or eliminate the ability to bind a wide range of receptors that mediate their effector functions in vivo. For example, recombinant molecules can be generated that combine the heavy and light chain variable regions of an antibody in a single protein that retains binding activity. Camels, alpacas and llamas make antibodies that express only a single variable domain, which can simplify the generation of engineered derivatives. The papers below also describe improved techniques to make bispecific antibodies, which simultaneously bind to two different surface molecules on the same tumor cell or to two different epitopes on the same cytokine, or even tri-specific reagents. Additional papers describe the generation of fusion proteins that combine antibody effector functions with recognition domains from other proteins, for example T cell receptors that recognize specific Major Histocompatibility Complex (MHC) proteins in association with antigenic peptides or MHC-peptide complexes themselves. Other, less easily classified systems and approaches illustrate how the flexibility of the basic antibody structure provides for directed natural selection to enhance affinity, as well as providing a backbone for tool building that allows the generation of valuable reagents. We hope you enjoy this collection.

The cover art shows that a synthetic antibody reported by Mukherjee et al. binds to the hinge region of its target, maltose-binding protein, explaining how it can be used to investigate the energetics of conformational change. Cover design by EJ Marklin.

Assembled by Peter Cresswell; published March 2020

Find more virtual issues

Modifications of effector functions

Bispecific (and more) antibodies

Fc hybrids with alternative ligands

Novel tools, single chain antibodies and directed evolution