The emerging role of biosensor-based epitope binning and mapping in antibody-based drug discovery.
BACKGROUND
Surface plasmon resonance (SPR) for affinity/kinetics measurements of drug candidates has been a mainstay application for characterizing drug candidates for many years. Recently, with the growth of monoclonal antibodies (mAbs) as a drug class and the availability of higher-throughput biosensors, the role of label-free biosensors has evolved to include epitope characterization in the early drug discovery process through epitope binning and mapping of mAbs.


METHODS
This manuscript outlines the importance of using epitope characterization early in the drug discovery process and describes a strategy for success in discovering drug leads. Updated practices for integrating epitope characterization with other biochemical/biophysical data, cell-based functional data, and computational prediction tools are also discussed.


CONCLUSIONS
The authors propose using epitope characterization during early drug discovery by: (1) using epitope binning of mAbs following the pre-screening of clones to assure selection of mAb candidates with epitope diversity, (2) binning the maximum number of mAbs in order to fully define epitope engagement profiles, and (3) integrating epitope binning/mapping data with binding affinity, kinetics, cell-based functional assays, etc. to better describe functional epitope. This approach, together with structural and binding prediction data, will improve the quality of leads and improve the selection speed for clinical candidates.
a Wasatch Microfluidics, Inc. , Salt Lake City , UT , USA.
Noah T
NT
Ditto
a Wasatch Microfluidics, Inc. , Salt Lake City , UT , USA.|b Electrical and Computer Engineering , North Dakota State University , Fargo , ND , USA.
Ben D
BD
Brooks
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015374:Biosensing Techniques / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000276:immunology; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007700:Kinetics; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D000939:Epitopes
Drug discovery; SPR; epitope; epitope binning; epitope mapping; high-throughput screening