title: Pre-existing Antibody: Biotherapeutic Modality-Based Review.
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.affiliation: Pfizer Worldwide Research & Development, PDM, 1 Burtt Rd, Andover, MA, USA. boris.gorovits@pfizer.com.
authors.forename: Boris
authors.identifier: http://orcid.org/0000-0001-9405-7718
authors.initials: B
authors.lastname: Gorovits
authors.affiliation: Janssen Research & Development, LLC (Johnson & Johnson), Welsh and McKean Roads, Spring House, PA, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Clements-Egan
authors.affiliation: Clinical Immunology, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Birchler
authors.affiliation: MedImmune, Clinical Pharmacology and DMPK, Mountain View, CA, USA.
authors.forename: Meina
authors.initials: M
authors.lastname: Liang
authors.affiliation: Bristol-Myers Squibb, Analytical & Bioanalytical Development, Princeton, NJ, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Myler
authors.affiliation: Genentech, BioAnalytical Sciences, San Francisco, CA, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Peng
authors.affiliation: UCB Celltech, Slough, UK.
authors.forename: Shobha
authors.initials: S
authors.lastname: Purushothama
authors.affiliation: Regeneron Pharmaceuticals, Inc. Bioanalytical Sciences, Tarrytown, NY, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Rajadhyaksha
authors.affiliation: DSAR, Project Standards and Innovation, Immunology and Biomarkers, Sanofi R&D, Framingham, MA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Salazar-Fontana
authors.affiliation: DSAR, Clinical Laboratory Sciences, Sanofi R&D, Framingham, MA, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Sung
authors.affiliation: Pfizer Worldwide Research & Development, PDM, 1 Burtt Rd, Andover, MA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xue
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001688:Biological Products / Q000097:blood* / Q000276:immunology; D001691:Biological Therapy / Q000379:methods*; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001688:Biological Products
keywords: anti-drug antibody; immunogenicity; pre-existing antibody
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