1042P - Rapid, single-step monitoring of circulating monoclonal antibodies using an aptamer-based electrochemical sensing platform

Background

Monoclonal antibodies (mAbs) have gained significant attention for various solid cancers. Better understanding inter-patient variability in mAbs' pharmacokinetics and pharmacodynamics is crucial for ensuring all patients effectiveness and acceptable toxicity. Increasing research in this area requires the development of low-cost, highly reproducible effective methods to measure blood concentrations of mAbs in single patients. We here present preliminary data of an in-house electrochemical DNA aptamer-based sensing platform on trastuzumab, a mAb targeting the Human Epidermal Growth Factor Receptor 2 (HER-2).

Methods

We developed an electrochemical platform for monitoring circulating mAbs levels. Leveraging the ability to easily attach various recognition elements to a synthetic nucleic acid sequence, a sensor capitalizing on the use of a structure-switching DNA aptamer as electrochemical bio-transducer for trastuzumab binding was developed. A methylene-blue labeled trastuzumab-binding DNA aptamer is covalently attached on the electrode surface and its molecular reconfiguration upon the binding of trastuzumab generates a concentration-dependent electrochemical readout. Blood samples (12) purchased for experimentation purposes were used and known concentrations of trastuzumab were added to test the assay. An Enzyme-linked immunosorbent assay (ELISA) was used as control test.

Results

We demonstrated the rapid (< 15 min), single-step detection of trastuzumab in blood samples. Trastuzumab concentration was quantified using both a commercial ELISA kit for the detection of free antibodies and the electrochemical assay. The ELISA results gave comparable results in terms of positive/negative discrimination (Cohen’s kappa = 0.729). The use of electrochemical biomolecular sensors based on DNA in a point-of-care drug monitoring system might represent an innovative tool for drug management.

Conclusions

The development of rapid, low-cost DNA-based assays hold great promise. These assays can shed light on the factors influencing inter-subject variability. Enhanced understanding of this variability should inform the refinement of dosing regimens, making them more tailored and effective.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R. Ergasti: Other, Institutional, Other: GSK, AZ. C. Nero: Other, Institutional, Speaker, Consultant, Advisor: GSK, Veeva, MSD, Altems; Other, Institutional, Sponsor/Funding: Illumina. C. Marchetti: Other, Institutional, Speaker, Consultant, Advisor: AZ, PharmaMar, GSK, MSD, Menarini. G. Ferrandina: Other, Institutional, Speaker, Consultant, Advisor: GSK, AZ, MSD, PharmaMar. G. Scambia: Other, Institutional, Speaker, Consultant, Advisor: Covidien AG, AZ, MSD, Olympus Europa, Baxter, Intuitive Surgical Inc., GSK. All other authors have declared no conflicts of interest.