Neutralizing antibody (NAb) (NAb)

Neutralizing antibodies (NAbs) are a subset of immunoglobulins produced by the host immune system that bind to specific epitopes on pathogens or foreign proteins, thereby preventing their interaction with cellular receptors and neutralizing their biological activity (NIH, 2020). While they provide essential protection against infectious diseases, NAbs represent a formidable challenge in the administration of biotherapeutics, such as enzyme replacement therapies and viral-vector-mediated gene therapies (Nature Reviews Drug Discovery, 2019). In these contexts, pre-existing or treatment-induced NAbs can bind to the therapeutic agent, leading to reduced efficacy, altered pharmacokinetics, or adverse immune-mediated reactions. Consequently, NAbs are increasingly treated as a target for modulation; for example, the enzyme imlifidase is used to rapidly cleave IgG antibodies, enabling life-saving organ transplants or gene therapy in patients who would otherwise be sensitized (New England Journal of Medicine, 2017). Strategies to monitor and mitigate the host NAb response are critical for the clinical success of biologics and the development of personalized medicine.

Other names

Host neutralizing antibodiesAnti-drug antibodyADAInhibitory antibodyNeutralizing immunoglobulin

Therapeutic intervention against host neutralizing antibodies involves the enzymatic degradation of existing immunoglobulins (e.g., imlifidase), the depletion of B-cell and plasma cell populations to halt production (e.g., rituximab, bortezomib), or the use of plasmapheresis to physically remove antibodies from circulation (Frontiers in Immunology, 2020).