title: A non-radioactive method for detecting neutralizing antibodies against therapeutic proteins in serum.
abstract: The presence of neutralizing antibodies against protein therapeutics continues to cause concern in the biomedical field. These antibodies not only reduce the efficacy of the protein therapeutics, but may also block the normal function of their endogenous counterparts, which can result in serious health risks to the patient. To date, a limited number of in vitro cell-based bioassays for detecting neutralizing antibodies against therapeutic proteins have been developed. However, many of the existing assays involve the use of radioactive materials. We have established a novel and non-radioactive bioassay system for detecting neutralizing antibodies in patient serum samples. Our assay measures the cell metabolic activities that are closely associated with cell proliferation and apoptosis. The biologic effect of the therapeutic protein and the capability of the antibodies to neutralize the therapeutics are reflected by changes of the cellular metabolic activities triggered by the administration of the therapeutics or presence of the anti-therapeutic protein antibodies. Compared with existing assays, this new assay is equally or more sensitive, and completely eliminates the use of radioactive materials.
authors.affiliation: Department of Clinical Immunology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors.forename: Iwona
authors.initials: I
authors.lastname: Wala
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Swanson
authors.forename: Shuqian
authors.initials: S
authors.lastname: Jing
mesh_terms: D000906:Antibodies / Q000097:blood*; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D009500:Neutralization Tests / Q000379:methods; D011994:Recombinant Proteins / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor