Antibody Structure and Function: The Basis for Engineering Therapeutics

By M. Chiu, Dennis R. Goulet, A. Teplyakov, Gary Gilliland. 2019

501 citations recorded by the source corpus.

Antibodies and antibody-derived macromolecules have established themselves as the mainstay in protein-based therapeutic molecules (biologics). Our knowledge of the structure–function relationships of antibodies provides a platform for protein engineering that has been exploited to generate a wide range of biologics for a host of therapeutic indications. In this review, our basic understanding of the antibody structure is described along with how that knowledge has leveraged the engineering of antibody and antibody-related therapeutics having the appropriate antigen affinity, effector function, and biophysical properties. The platforms examined include the development of antibodies, antibody fragments, bispecific antibody, and antibody fusion products, whose efficacy and manufacturability can be improved via humanization, affinity modulation, and stability enhancement. We also review the design and selection of binding arms, and avidity modulation. Different strategies of preparing bispecific and multispecific molecules for an array of therapeutic applications are included.

Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging

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Citations in the corpus

AFsample: improving multimer prediction with AlphaFold using massive sampling (2023, background): “Target H1144 is a nanobody interaction, nanobodies and regular antibody interactions are particularly challenging to model since the interaction with the antigen is highly specific, and the exact shape and location of the epitopes can vary significantly depending on the antigen (Chiu et al. 2019).”
Observed Antibody Space: A diverse database of cleaned, annotated, and translated unpaired and paired antibody sequences (2021, background): “Further diversity is introduced by somatic hypermutation, especially in the three complementarity determining regions of each chain (shown in black in Figure 1).(3,4) Due to the high variability of the binding site, antibodies have the ability to bind with high affinity and specificity to almost any”
Improved antibody structure prediction by deep learning of side chain conformations (2021, background): “The surface of the antibody CDR loops including the side chains play an important role in antigen recognition [7].”