A Surface Plasmon Resonance-based assay to measure serum concentrations of therapeutic antibodies and anti-drug antibodies

Abstract

Therapeutic drug and immunogenicity monitoring (TDIM) is increasingly proposed to guide therapy with biologics, characterised by high inter-individual variability of their blood levels, to permit objective decisions for the management of non-responders and reduce unnecessary interventions with these expensive treatments. However, TDIM has not yet entered clinical practice partly because of uncertainties regarding the accuracy and precision of enzyme-linked immunosorbent assays (ELISA). Here we report the characterisation of a novel surface plasmon resonance (SPR)-based TDIM, applied to the measurement of serum concentrations of infliximab, an antibody against tumour necrosis factor α (anti-TNFα), and anti-infliximab antibodies. SPR has the obvious advantages of directly detecting and measuring serum antibodies in minutes, avoiding the long incubation/separation/washing/detection steps of the methods proposed so far, reducing complexity and variability. Moreover, drug and anti-drug antibodies can be measured simultaneously. This new method was validated for sensitivity and reproducibility, and showed cost-effectiveness over commercial ELISA kits. This method may be applied to other biotherapeutics. These data pave the way for the development of SPR-based point-of-care devices for rapid on-site analysis.

Characterization of the neutralizing anti‐emicizumab antibody in a patient with hemophilia A and inhibitor

“…The flow channels can be rotated 90°, thus creating a 36‐spot interaction array. For this study, emicizumab and control IgG were immobilized using amine‐coupling chemistry on parallel lanes of the same GLC sensor chip (Bio‐Rad) 22,23 . The surface was activated with sulfo‐NHS/EDC according to the manufacturer's recommendation.…”

Optical biosensors - Illuminating the path to personalized drug dosing

“…The potential for SPR to be used in multiplex measurements has also been demonstrated. One key illustration of this is the simultaneous detection of infliximab and the anti-IFX antibody (Beeg et al, 2019). These were detected using a microfluidic chip with tumor necrosis factor α (ligand for infliximab detection) and infliximab (ligand for the antibody detection) immobilized onto flow channels.…”

Recent progress in the molecular imaging of therapeutic monoclonal antibodies

“…Surface plasmon resonance (SPR) biosensor has the obvious advantages of directly detecting and measuring serum antibodies in minutes; avoiding the long incubation, separation, washing or detection steps; and reducing complexity and variability [ 53 ]. Recently, Gobbi’s group [ 54 ] developed a method to measure mAbs based on SPR. The apparatus has six flow channels which can immobilize up to six ligands; then the flow channels can be rotated 90° so that up to six serum samples can be flowed in parallel ( Fig.…”