Rapid, Single-Step Monitoring of Monoclonal Antibody Bioavailability by Using a TNF-α-Based Multiepitope DNA...

Area of Science:

• Biotechnology
• Immunology
• Pharmacology

Background:

• Therapeutic drug monitoring (TDM) is crucial for personalized therapy in chronic inflammatory diseases.
• Monoclonal antibodies (mAbs) are key treatments but can be affected by antidrug antibodies (ADAs), reducing efficacy.
• Current monitoring methods can be time-consuming and lack sensitivity to ADA impact.

Purpose of the Study:

• To develop a rapid, homogeneous, and affinity-based assay for TDM of therapeutic mAbs.
• To utilize a programmable nanosensor platform (NanoHYBRID) for detecting multiple mAbs targeting distinct epitopes.
• To assess the platform's sensitivity to ADAs and its utility in monitoring bioavailable mAb levels.

Main Methods:

• Development of a fluorescence-based programmable nanosensor (NanoHYBRID platform) using Tumor Necrosis Factor α (TNF-α) as a binding moiety.
• Direct conjugation of TNF-α to DNA probes for a homogeneous, one-step assay.
• Detection of therapeutic mAbs (Infliximab, Adalimumab, Golimumab) and ADAs in human serum samples.

Main Results:

• The NanoHYBRID platform successfully detected therapeutic concentrations of clinically relevant mAbs in a single step.
• The sensor demonstrated heightened sensitivity to ADAs, impacting drug quantification and indicating utility for monitoring bioavailable drug levels.
• Compared to ELISA, the NanoHYBRID platform showed superior sensitivity to ADAs.

Conclusions:

• The NanoHYBRID platform provides a rapid, sensitive, and modular solution for TDM of therapeutic mAbs.
• Its ability to detect ADAs and monitor bioavailable drug levels offers advantages over traditional methods like ELISA.
• This technology has the potential to improve personalized therapy management for patients with chronic inflammatory diseases.