title: Preclinical models used for immunogenicity prediction of therapeutic proteins.
abstract: All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences-UIPS, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors: Vera
authors: V
authors: Brinks
authors: Daniel
authors: D
authors: Weinbuch
authors: Matthew
authors: M
authors: Baker
authors: Yann
authors: Y
authors: Dean
authors: Philippe
authors: P
authors: Stas
authors: Stefan
authors: S
authors: Kostense
authors: Bonita
authors: B
authors: Rup
authors: Wim
authors: W
authors: Jiskoot
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008954:Models, Biological; D011506:Proteins / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D011506:Proteins
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