This study develops a novel lateral flow immunoassay platform (SBFIA) enabling rapid, sensitive detection of neutralizing antidrug antibodies (nαIFX) with superior drug tolerance and specificity. The platform employs a sequential binding strategy to effectively eliminate drug interference, demonstrating potential for point-of-care testing (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 antidrug antibodies (nαIFX) induced by anti-tumor necrosis factor (TNF) monoclonal antibody therapies like infliximab (IFX). The research focuses on developing a rapid detection method without acid dissociation pretreatment to enhance clinical decision-making accuracy and timeliness.
Background Knowledge
Infliximab is a widely used TNF inhibitor for treating autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. However, long-term treatment may induce antidrug antibodies (ADA), particularly neutralizing antidrug antibodies (nαIFX), which accelerate drug clearance and reduce therapeutic efficacy. Conventional methods like ELISA and electrochemiluminescence (ECL) exhibit drug susceptibility requiring acid dissociation steps, limiting their clinical applicability. While lateral flow assays (LFA) offer convenience, they have yet to effectively differentiate nαIFX from drug-bound states. The proposed SBFIA platform addresses these limitations through sequential binding principles combined with chemiluminescent detection, providing new insights for rapid point-of-care testing.
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. This was combined with a reporter (R)-labeled anti-human IgG antibody, further implementing a three-zone binding strategy using TNF, IFX, and anti-human Fc antibody (AHFc) on nitrocellulose membranes for nαIFX detection in complex samples. During optimization, the team adjusted IFX immobilization zone quantity and concentration to minimize background signals while enhancing detection sensitivity.
Key Conclusions and Perspectives
Research Significance and Prospects
This study introduces a rapid, portable, and sensitive method for antidrug antibody detection suitable for point-of-care testing (POC), significantly shortening clinical decision-making timelines. Future research will focus on optimizing platform stability and expanding its application to other monoclonal antibody therapies, promoting personalized treatment strategies.
Conclusion
This paper presents an innovative lateral flow immunoassay platform (SBFIA) capable of specifically and sensitively detecting neutralizing antidrug antibodies (nαIFX) without acid dissociation pretreatment. Utilizing sequential binding strategies, the platform effectively eliminates drug interference while demonstrating superior drug tolerance and specificity. Compared to traditional ELISA, SBFIA offers significant advantages in detection speed, operational convenience, and clinical applicability, particularly for rapid diagnostics and personalized treatment decisions. This research provides a new direction for antidrug antibody detection and establishes a foundation for advancing point-of-care testing (POC) technologies. The platform could potentially expand to multiple monoclonal antibody therapies through bioreceptor replacement in future applications.
