Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics

• Published in: Journal of immunological methods Vol. 321; no. 1; pp. 1 - 18
• Main Authors: Gupta, Shalini, Indelicato, Stephen R., Jethwa, Vijay, Kawabata, Thomas, Kelley, Marian, Mire-Sluis, Anthony R., Richards, Susan M., Rup, Bonita, Shores, Elizabeth, Swanson, Steven J., Wakshull, Eric
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.04.2007; Elsevier
• Subjects: Animals; Antibodies - analysis; Antibodies - immunology; Biological and medical sciences; Biological Assay - methods; Biological Assay - standards; Biological Products - immunology; Biological Products - therapeutic use; Calibration; Cell Line; Cell-based assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Guidelines as Topic; Humans; Immunoassay - methods; Immunoassay - standards; Immunogenicity assay; Molecular immunology; NAb assay; Neutralization Tests - methods; Neutralizing antibody bioassay; Reference Standards; Reproducibility of Results; Research Design; Sensitivity and Specificity; Serum-based bioassay; Techniques; EPO; PRCA; SPA; Immunogenicity assay; mRNA; FACS; MTT; TNF; NAb; MAb; GFP; HSA; Cell-based assay; EIA; Neutralizing antibody bioassay; IL-1; RIA; KIRA; ECL; rHuEPO; Serum-based bioassay; CV; CAT; MGDF; NAb assay; BrdU; Ig; ELISA; Bioassay; Immune response; Neutralizing antibody; Optimization; Immunological method; Biological compound; Immunogenicity; Serum; Detection; Humoral immunity
• ISSN: 0022-1759; 1872-7905
• DOI: 10.1016/j.jim.2006.12.004

The administration of biological therapeutics can evoke some level of immune response to the drug product in the receiving subjects. An immune response comprised of neutralizing antibodies can lead to loss of efficacy or potentially more serious clinical sequelae. Therefore, it is important to monitor the immunogenicity of biological therapeutics throughout the drug product development cycle. Immunoassays are typically used to screen for the presence and development of anti-drug product antibodies. However, in-vitro cell-based assays prove extremely useful for the characterization of immunoassay-positive samples to determine if the detected antibodies have neutralizing properties. This document provides scientific recommendations based on the experience of the authors for the development of cell-based assays for the detection of neutralizing antibodies in non-clinical and clinical studies.