Detection of Low-Affinity Anti-Drug Antibodies and Improved Drug Tolerance in Immunogenicity Testing by Octet Biolayer Interferometry

Li, J., et al., 54(2), 286-294, J Pharm Biomed Anal, 2010

The authors compare performance of the Octet system to ELISA and MSD techniques for detection of anti-drug antibodies (ADA) against an investigational therapeutic human IgG1 mAb called CNTO X. They found that the Octet platform assay was the most sensitive and ELISA the least sensitive for detection of low-affinity ADAs. The assay also tolerated the presence of free drug to 10X greater levels than the MSD assay, and 100X greater levels than the ELISA assay. The MSD and Octet platform assays were applied to the bioanalysis of cynomolgus monkey sera from a pre-clinical multiple dose study of CNTO X. The Octet system indicated 3 positive animals developed ADA as early as day 15 of the dosing phase while drug was present at nearly 1 mg/mL. ECLIA detected only one of these, and only in a day 57 recovery sample after drug had cleared from circulation. The authors conclude that the Octet instrument is a promising platform for detection of lower affinity ADAs and is particularly suitable for ADA detection when drug persists at levels that negatively impact bridging immunoassays.

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