A competitive ligand binding assay for detection of neutralizing antibodies against an insulin analog.

Autor: Peek VL; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA., Lemen DM; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA., Konrad RJ; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA., Wen Y; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. Electronic address: wen_yi1@lilly.com.
Jazyk: angličtina
Zdroj: Journal of immunological methods [J Immunol Methods] 2023 Dec; Vol. 523, pp. 113575. Date of Electronic Publication: 2023 Oct 14.
DOI: 10.1016/j.jim.2023.113575
Abstrakt: Biotherapeutics have the potential to trigger undesired immune responses in the patients. For therapeutic proteins, immunogenicity is manifested as anti-drug antibodies (ADA). Because ADA could compromise pharmacokinetics, efficacy, and safety, regulatory agencies require immunogenicity assessment during clinical development. A tiered bioanalytical approach is recommended to monitor clinical immunogenicity, and neutralizing antibodies (NAb) are studied in Tier 4 if the molecule is immunogenic. Although cell-based assays, which reflect the pharmacological mechanism of action, are in some cases the preferred assay format for detecting NAbs, they are associated with operational complexity and sometimes suboptimal assay performance. Alternatively, non-cell-based assays have also been developed and implemented. In our current study, a competitive ligand binding assay (CLBA) was developed to detect NAbs for insulin efsitora alfa (efsitora, basal insulin Fc, LY3209590), a novel fusion protein being studied for the treatment of Type 1 diabetes and Type 2 diabetes. The CLBA demonstrated acceptable sensitivity, drug tolerance, precision, and robustness, and thus provides a suitable approach for detecting NAbs against efsitora.
Competing Interests: Declaration of Competing Interest All authors are employees of Eli Lilly and Company or its subsidiary at the time of the work described here.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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