Pre-existing Antibody: Biotherapeutic Modality-Based Review

Pre-existing antibodiesto biotherapeutic drugs have been detected in drug-naivesubjects for a variety of biotherapeutic modalities. Pre-existing antibodiesare immunoglobulins that are either specific or cross-reacting with a protein or glycanepitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodiesis often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodiesvary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodiesare viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodiesare reviewed. Initial evidence for pre-existing antibodyis often identified during anti-drug antibody(ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed.