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

Marten Beeg,Daniela Gilardi,Silvio Danese,Gionata Fiorino,Silvio Garattini,Mario Salmona,Marco Gobbi,Francesca Rogai,Barbara Orsini,Alessandro Nobili

doi:10.1038/s41598-018-37950-4

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.

Highlights

Therapeutic antibodies are one of the most innovative and fastest growing segments in the pharmaceutical industry[1], promoted by the continuous progress of molecular engineering technologies[2]
Patients who continue to have loss of response (LOR) are usually switched to a different anti-tumour necrosis factor α (TNFα) antibody, assuming the presence of antibodies towards IFX (ATI), or they are switched to another class of agents
All but one of these ATI-positive serum samples were ATI-positive with surface plasmon resonance (SPR) as well; SPR detected ATI in a serum considered ATI-negative by enzyme-linked immunosorbent assays (ELISA)

Summary

Introduction

Therapeutic antibodies are one of the most innovative and fastest growing segments in the pharmaceutical industry[1], promoted by the continuous progress of molecular engineering technologies[2]. SPR has significant advantages: TNFα and IFX are immobilised, as “capturing” molecules, on parallel surfaces of the same sensor chip, and the flow of patient’s sera on both of them results in immediate SPR signals, from which IFX and ATI concentrations are determined simultaneously, on the calibration curves.

Results

Conclusion