title: Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges.
abstract: The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule, and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review, we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, RA Leiden 2300, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, RA Leiden 2300, The Netherlands.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kijanka
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado - Boulder, Boulder, Colorado 80309.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Randolph
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Pharmaceutical Sciences, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: John F
authors.initials: JF
authors.lastname: Carpenter
authors.affiliation: Pharma Technical Development (Europe) Biologics, Basel 4070, Switzerland.
authors.forename: Atanas V
authors.initials: AV
authors.lastname: Koulov
authors.affiliation: Pharma Technical Development (Europe) Biologics, Basel 4070, Switzerland.
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: Amgen Inc., Process Development, Thousand Oaks, California 91320.
authors.forename: Marisa K
authors.initials: MK
authors.lastname: Joubert
authors.affiliation: Amgen Inc., Medical Sciences, Thousand Oaks, California 91320.
authors.forename: Vibha
authors.initials: V
authors.lastname: Jawa
authors.affiliation: Amgen Inc., Process Development, Thousand Oaks, California 91320. Electronic address: lnarhi@amgen.com.
authors.forename: Linda O
authors.initials: LO
authors.lastname: Narhi
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D055261:Immunogenetic Phenomena / Q000502:physiology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007162:Immunoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D066329:Protein Aggregates / Q000235:genetics / Q000276:immunology; D013045:Species Specificity
chemical_list: D007074:Immunoglobulin G; D007162:Immunoproteins; D066329:Protein Aggregates
keywords: immunogenicity; in vivo models; protein aggregation