Pre-existing Antibody: Biotherapeutic Modality-Based Review
Journal Title: The AAPS Journal - Year 2016, Vol 18, Issue 2
Abstract
Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary 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 antibodies are 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 antibodies are reviewed. Initial evidence for pre-existing antibody is 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.
Authors and Affiliations
Boris Gorovits, Adrienne Clements-Egan, Mary Birchler, Meina Liang, Heather Myler, Kun Peng, Shobha Purushothama, Manoj Rajadhyaksha, Laura Salazar-Fontana, Crystal Sung, Li Xue
Keywords
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