This study developed a novel Sequential Binding Flow Immunoassay (SBFIA) platform capable of rapid, sensitive detection of neutralizing anti-infliximab antibodies (nαIFX) with superior drug tolerance and specificity. Through sequential binding strategies, the platform effectively eliminates drug interference, making it suitable for point-of-care (POC) applications.
Literature Overview
The article 'Drug-Tolerant, Chemiluminescent Lateral Flow Immunoassay Platform for the Determination of Neutralizing Anti-Drug Antibodies' published in Small reviews recent technological advancements in detecting neutralizing anti-TNF monoclonal antibody drug antibodies (nαIFX) induced by infliximab (IFX). The research focuses on developing rapid detection methods without acid dissociation pretreatment to improve clinical decision-making accuracy and timeliness.
Background Knowledge
Infliximab (IFX) is a widely used TNF inhibitor for treating autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. However, long-term therapy may induce anti-drug antibodies (ADA), particularly neutralizing anti-infliximab antibodies (nαIFX), which accelerate drug clearance and reduce therapeutic efficacy. Conventional methods like ELISA and electrochemiluminescence (ECL) face drug sensitivity challenges requiring acid dissociation steps, limiting their point-of-care applications. While lateral flow immunoassays (LFA) offer operational convenience, they have failed to effectively distinguish nαIFX in drug-bound states. The proposed SBFIA platform employs sequential binding principles combined with chemiluminescent detection to overcome these limitations, providing a new approach for point-of-care diagnostics.
Research Methods and Experiments
The research team developed a Sequential Binding Flow Immunoassay (SBFIA) platform by immobilizing infliximab (IFX) on the sample pad (SP) to capture free nαIFX, followed by introducing a reporter labeled with anti-human IgG antibody. A three-zone binding strategy utilizing TNF, IFX, and anti-human Fc antibody (AHFc) was implemented on the nitrocellulose membrane to enable detection of nαIFX in complex samples. During optimization, the team adjusted immobilization zone quantity and IFX concentration to reduce background signals and enhance sensitivity.
Key Conclusions and Perspectives
Research Significance and Prospects
This study introduces a rapid, portable, and sensitive ADA detection method applicable to point-of-care (POC) diagnostics, significantly reducing clinical decision-making time. Future research will optimize platform stability and expand its application to other monoclonal antibody therapies, advancing personalized medicine strategies.
Conclusion
This paper presents an innovative lateral flow immunoassay platform (SBFIA) for specific, sensitive detection of neutralizing anti-drug antibodies (nαIFX) without acid dissociation pretreatment. By utilizing sequential binding strategies, the platform effectively eliminates drug interference while maintaining excellent drug tolerance and specificity. Compared to conventional ELISA, SBFIA offers significant advantages in detection speed, operational simplicity, and clinical applicability, particularly for point-of-care diagnostics and personalized treatment monitoring. The platform establishes a foundation for future POC technology development and can be extended to immunogenicity monitoring of various monoclonal antibody therapies through bio-receptor replacement.
