Overcoming soluble target interference in an anti-therapeutic antibody screening assay for an antibody–drug conjugate therapeutic. (August 2012)

• Record Type: Journal Article
• Authors: Carrasco-Triguero, Montserrat; Mahood, Connie; Milojic-Blair, Marija; Amaya, Caroline; Ruppel, Jane; Hong, Kyu; Yi, Joo-Hee; Kaur, Surinder
• Is Part Of: Bioanalysis. Volume 4:Number 16(2012)
• Page Start: 2013
• Page End: 2026
• Publication Date: 2012-08
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.12.165
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: The standard safety evaluation of biotherapeutics includes assessment of immunogenicity. Anti-therapeutic antibodies (ATA) can be detected in serum using immunoassays with a bridging format. However, these assays can be subject to interference.Results: In the bridging ATA assay for 3A5 TDC, an antibody–drug conjugate that binds to the multimeric extracellular domain of MUC16 (CA125), soluble CA125 in the serum caused false-positive results by binding to the ATA assay reagents. This interaction was blocked by wheat germ agglutinin lectin as it binds to the glycans in CA125; thus, the specificity of the assay improved.Conclusion: The assay development and validation results showed that the addition of wheat germ agglutinin eliminates the interference from circulating CA125 without impacting the ability to detect ATA.