Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics.
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.
Gupta
Shalini
S
Clinical Immunology, Amgen Inc., Thousand Oaks, CA 91320, USA. shalinig@amgen.com
Indelicato
Stephen R
SR
Jethwa
Vijay
V
Kawabata
Thomas
T
Kelley
Marian
M
Mire-Sluis
Anthony R
AR
Richards
Susan M
SM
Rup
Bonita
B
Shores
Elizabeth
E
Swanson
Steven J
SJ
Wakshull
Eric
E
D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000276:immunology; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D001688:Biological Products / Q000276:immunology* / Q000627:therapeutic use; D002138:Calibration; D002460:Cell Line; D017408:Guidelines as Topic; D006801:Humans; D007118:Immunoassay / Q000379:methods* / Q000592:standards; D009500:Neutralization Tests / Q000379:methods; D012015:Reference Standards; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity
D000906:Antibodies; D001688:Biological Products