Bartek Zuber: Immunogenicity assessment for Affibody-Fc fusion therapeutics

Описание: Mastering Immunity Europe 2017

SOBI is developing novel biopharmaceutical drugs based on the antibody-like Affibody scaffold. The molecules are fusion proteins composed of target specific Affibody domains of non-human origin, fused to the human IgG1-Fc for half-life extension. The E. coli produced non-glycosylated Fc fusions are devoid of Fc-gamma receptor and C1q mediated effector functions but still retain FcRn-mediated recycling with associated decreased clearance. In the screening process to select the most promising drug candidates, a multi-tiered approach was used to evaluate immunogenicity of Affibody-Fc fusion proteins. Several in silico platforms were used for a broad primary screening. Next we investigated which peptides were presented on MHC-II after protein uptake and processing by dendritic cells (DCs). Predicted or presented peptides, protein domains or full-length proteins were next used to stimulate CD4+ T-cells using PBMCs or DC:T assays. The selected candidates had a DC:T assay response-index similar to therapeutic grade human antibodies or human Fc indicating low immunogenicity.

Dr Zuber is a Senior Scientist Translational Sciences, Swedish Orphan Biovitrum AB, Sweden and has 20 years’ experience of immune response modulation. He has worked with enhancement of vaccine induced responses and deimmunization of protein therapeutics. He is also experienced in development and immunotoxicity assessment of therapeutic proteins.