Neutralising Antibody
An anti-drug antibody that binds to the active site of a therapeutic peptide, directly preventing it from interacting with its biological target. Neutralising antibodies are the most clinically significant form of immunogenicity because they can completely abolish a drug's therapeutic effect.
Technical Context
Neutralising antibody assays use either cell-based functional assays (measuring whether ADA-containing serum blocks the drug's ability to activate its receptor in a cell system) or competitive ligand-binding assays (measuring whether ADA blocks drug-receptor binding). Cell-based assays are more physiologically relevant but technically demanding. The clinical threshold for clinically significant neutralisation varies by drug — low-titre transient NAbs may have no clinical impact, while high-titre persistent NAbs can render treatment ineffective. For biosimilar development, comparative immunogenicity (ADA/NAb incidence and clinical impact in the biosimilar vs reference product) is a key regulatory requirement. Risk mitigation strategies include: humanising peptide sequences, removing T-cell epitopes (deimmunisation), optimising formulation to minimise aggregation, and selecting administration routes with lower immunogenicity risk.