A neutralizing antibody (NAb) is an antibody that defends a cell from an antigen or infectious body by neutralizing any effect it has biologically. NAbs against therapeutic proteins or peptides can significantly decrease the efficacy of these drug candidates, which is why NAb test serves as a crucial aspect in immunogenicity test.
Generally, FDA considers that bioassays are more reflective of the in vivo situation and are recommended. For NAb assays, the bioassay should be related to mechanism of action, otherwise the assays will not be informative enough as to the effect of NAbs on clinical results. The development and validation of neutralization assays are difficult and vary dramatically between different samples. Nonetheless, cell based assays are still recommended because they are critical to understanding the importance of patient immune responses to therapeutic proteins.
Cell-based NAb assay designs utilize intracellular signaling events triggered by the drug candidates or the ligand inhibited by the drug candidates, and may also utilize study of extracellular binding events at the cell surface. The frequently-used readouts for Profacgen’s NAb cell based assays include: cell proliferation, biomarker, reporter gene expression, antibody- dependent cell-mediated cytotoxicity (ADCC), etc.
The followings are provided by Profacgen for conducting a cell-based NAb assay for a given sample:
Because of limitations for cell based assays (suitable cell line, interference, specificity, sensitivity, etc.), once neutralizing cell-based assays are not feasible for your sample, Profacgen can also provide competitive ligand binding assays or alternative assay methods. All these methods been verified for their reflection of neutralizing capacity/potential.
Please feel free to contact us if you are interested in or have any questions for our NAb test service.