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Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum
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Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum
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Paper
Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum
2021
Overview
The ability to characterize the binding kinetics of drug-target interactions in a biologically relevant matrix, such as serum or plasma, remains a fundamental challenge in drug discovery. We apply a novel label-based giant magnetoresistance (GMR) biosensor platform to measure protein binding kinetics and affinities of drug-target pairs in buffer and different levels of serum. Specifically, we evaluate three well-established immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab and compare the results with label-free kinetic platforms: surface plasmon resonance (SPR) and bio-layer interferometry (BLI). Labeling of analytes does not affect their association and dissociation rates (on and off rates) from GMR biosensors which enables kinetic measurements in biologically relevant matrices. Only the GMR biossensors is consistently suitable for measuring binding kinetics in up to 80% serum. The faster and different off-rates of the three immune checkpoint inhibitors in the presence of serum should be considered when modeling their pharmacological performance. Competing Interest Statement DY, HY, SJO, MLC and KC are employees of MagArray, Inc. ABK is a consultant for MagArray, Inc. and SXW has stock options in MagArray Inc, which has licensed relevant patents from Stanford University for commercialization of GMR biosensor technology. TS is an employee of Hitachi High-Tech Corp.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
