title: Coupling of aggregation and immunogenicity in biotherapeutics: T- and B-cell immune epitopes may contain aggregation-prone regions.
abstract: Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.
authors: Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., MC6S, 575 Maryville Centre Drive, St. Louis, Missouri 63141, USA. Sandeep.Kumar@Pfizer.com
authors: Sandeep
authors: S
authors: Kumar
authors: Satish K
authors: SK
authors: Singh
authors: Xiaoling
authors: X
authors: Wang
authors: Bonita
authors: B
authors: Rup
authors: Davinder
authors: D
authors: Gill
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products / Q000276:immunology* / Q000627:therapeutic use; D055808:Drug Discovery; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011506:Proteins / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D001688:Biological Products; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D011506:Proteins