%0 Journal Article
%T Pre-existing Antibody: Biotherapeutic Modality-Based Review
%A Adrienne Clements-Egan
%A Boris Gorovits
%A Crystal Sung
%A Heather Myler
%A Kun Peng
%A Laura Salazar-Fontana
%A Li Xue
%A Manoj Rajadhyaksha
%A Mary Birchler
%A Meina Liang
%A Shobha Purushothama
%J Archive of "The AAPS Journal".
%D 2016
%R 10.1208/s12248-016-9878-1
%X Pre-existing antibodies to biotherapeutic drugs have been detected in drug-na£żve 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
%K anti-drug antibody
%K immunogenicity
%K pre-existing antibody
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779092/