title: Immunogenicity of Therapeutic Protein Aggregates.
abstract: Therapeutic proteins have a propensity for aggregation during manufacturing, shipping, and storage. The presence of aggregates in protein drug products can induce adverse immune responses in patients that may affect safety and efficacy, and so it is of concern to both manufacturers and regulatory agencies. In this vein, there is a lack of understanding of the physicochemical determinants of immunological responses and a lack of standardized analytical methods to survey the molecular properties of aggregates associated with immune activation. In this review, we provide an overview of the basic immune mechanisms in the context of interactions with protein aggregates. We then critically examine the literature with emphasis on the underlying immune mechanisms as they relate to aggregate properties. Finally, we highlight the gaps in our current understanding of this issue and offer recommendations for future research.
authors: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907.
authors: Ehab M
authors: EM
authors: Moussa
authors: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907.
authors: Jainik P
authors: JP
authors: Panchal
authors: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907.
authors: Balakrishnan S
authors: BS
authors: Moorthy
authors: Department of Microbiology and Immunology, School of Medicine, Indiana University, Indianapolis, Indiana 46202.
authors: Janice S
authors: JS
authors: Blum
authors: Amgen Inc., Process Development, Thousand Oaks, California 91320.
authors: Marisa K
authors: MK
authors: Joubert
authors: Amgen Inc., Process Development, Thousand Oaks, California 91320.
authors: Linda O
authors: LO
authors: Narhi
authors: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907. Electronic address: topp@purdue.edu.
authors: Elizabeth M
authors: EM
authors: Topp
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D002986:Clinical Trials as Topic / Q000379:methods; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D055261:Immunogenetic Phenomena; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D066329:Protein Aggregates / Q000276:immunology*
chemical_list: D016207:Cytokines; D066329:Protein Aggregates
keywords: immune response; physicochemical properties; protein aggregation; proteins; regulatory science