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Antibody Structure and Function: The Basis for Engineering Therapeutics

https://www.mdpi.com/2073-4468/8/4/55

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Antibody Structure and Function: The Basis for Engineering Therapeutics

by Mark L. Chiu 1,*ORCID,Dennis R. Goulet 2ORCID,Alexey Teplyakov 3 andGary L. Gilliland 3

1

Drug Product Development Science, Janssen Research & Development, LLC, Malvern, PA 19355, USA

2

Department of Medicinal Chemistry, University of Washington, P.O. Box 357610, Seattle, WA 98195-7610, USA

3

Biologics Research, Janssen Research & Development, LLC, Spring House, PA 19477, USA

*

Author to whom correspondence should be addressed.

Antibodies 2019, 8(4), 55; https://doi.org/10.3390/antib8040055

Received: 16 October 2019 / Revised: 25 November 2019 / Accepted: 28 November 2019 / Published: 3 December 2019

(This article belongs to the Special Issue Structure and Function of Antibodies)

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Abstract

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.

Keywords: antibody engineering; therapeutic biologics