Prevalence and Isotypic Complexity of the Anti-Chinese Hamster Ovary Host Cell Protein Antibodies in Normal Human Serum
Journal Title: The AAPS Journal - Year 2010, Vol 12, Issue 1
Abstract
Host cell-derived protein impurities may be present at low levels in biopharmaceutical products. Antibodies to host cell proteins are present in individuals with no known exposure to these products. In this study, antibodies to drug process-specific Chinese hamster ovary host cell-derived proteins (CHO-HCP) were measured in unexposed individuals using a validated enzyme-linked immunosorbent assay. Samples that tested positive for anti-CHO-HCP reactivity were further characterized to determine the isotypes and IgG subclasses expressed in each positive individual. The specificity of the detected anti-CHO-HCP antibody isotypes was confirmed by the competitive inhibition assay and the uncoated plate specificity testing. These antibody characterization experiments revealed that the prevalent anti-CHO-HCP antibody subclasses were predominantly IgG1 (present in 66.6% of individuals) and IgG2 (60%), with 33.3% positive for IgG3 while IgG4 was detected in low abundance. Forty percent (40%) of the individuals with IgG type reactivity were also identified as IgM-positive. Anti-CHO-HCP-specific IgE was not detected in the assays used in this study. Some individuals exhibited single isotype anti-CHO-HCP reactivity; others contained a combination of multiple antibody isotypes. Data presented in this study demonstrate the isotypic complexity and the high prevalence of anti-CHO-HCP antibodies in human serum with no known exposure to CHO cell-derived therapeutic biologics.
Authors and Affiliations
Li Xue, Rasheeda Johnson, Boris Gorovits
Keywords
Related Articles
- EP ID EP681355
- DOI 10.1208/s12248-009-9165-5
- Views 62
- Downloads 0
Pilot and Repeat Trials as Development Tools Associated with Demonstration of Bioequivalence
The online version of this article (doi:10.1208/s12248-015-9744-6) contains supplementary material, which is available to authorized users.
Comparison of stepwise covariate model building strategies in population pharmacokinetic-pharmacodynamic analysis
The aim of this study was to compare 2 stepwise covariate model-building strategies, frequently used in the analysis of pharmacokinetic-pharmacodynamic (PK-PD) data using nonlinear mixed-effects models, with respect to i...
Small-molecule agonists and antagonists of the opioid receptor-like receptor (ORL1, NOP): Ligand-based analysis of structural factors influencing intrinsic activity at NOP
The recently discovered fourth member of the opioid receptor family, the nociceptin receptor (NOP) and its endogenous ligand, the heptadecaptide nociceptin, are involved in several central nervous system pathways, such a...
Choice of LC-MS Methods for the Absolute Quantification of Drug-Metabolizing Enzymes and Transporters in Human Tissue: a Comparative Cost Analysis
The online version of this article (doi:10.1208/s12248-014-9712-6) contains supplementary material, which is available to authorized users.
Synthesis and Pharmacological Evaluation of 6-Acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), a Cocaine Antagonist, in Rodents
The online version of this article (doi:10.1208/s12248-011-9274-9) contains supplementary material, which is available to authorized users.