Steffen Kreye
Glycotope GmbH, Germany
Title: Using GlycoExpress for production of highly active antibodies directed against novel and existing targets
Biography
Steffen Kreye is a leading scientist at Glycotope GmbH. He is responsible for the development and optimization of the in-house developed and FDA-approved GlycoExpress cell line through metabolic engineering as well as the improvement of the established GlycoProcess. Since 2012 he is part of Glycotope’s Upstream Process Development Group. Before the appointment at Glycotope, he studied Biotechnology at the University of Technology in Braunschweig, where he gained his Bachelor and Master of Science. His Masters included a year-long exchange at the University of Waterloo, Canada.
Abstract
Glycosylation is one of the major post-translational modifications of bio-therapeutics important for bioactivity, bioavailability, immunogenicity and patient coverage. By establishment of the GlycoExpressâ„¢ toolbox (GEXâ„¢) we have generated a set of glycol-engineered human cell lines for the high yield production of fully human glycoproteins to optimize the glycosylation of antibodies and non-antibody bio-therapeutics for improvement of the clinical efficacy and side effects. The system is biotechnologically superior in quality, reproducibility and yield compared to other, including conventional production systems. All four clinical products derived from GlycoExpress cells are produced using a perfusion bioreactor system in order to assure highest possible product quality and reproducibility combined with high yield production. Cells are kept in the optimal growing and production phase over the production process which leads to highly stable product quality allowing a flexible duration of the run in one batch size, in combination with stable high productivity of the cells over time. Furthermore the product qualities produced in different scales ranging from 1 L to 200 L bioreactors are highly comparable.
Anna D Koromyslova
Heidelberg University, Germany
Title: A new tool for detecting and destroying norovirus
Biography
Anna D Koromyslova graduated with honors from Lomonosov Moscow State University, Russia in 2012. After graduation she worked as a Research Engineer at Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of RAS, Moscow, Russia. Since 2013 she is a Postdoctoral student in Heidelberg University and German Cancer Research Center, Germany. She is the author of five scientific papers, one of which was recently spotlighted in Journal of Virology, ASM.
Abstract
Noroviruses are positive-sense, single-stranded RNA viruses and are a major cause of gastroenteritis worldwide. Norovirus capsid protein can be subdivided into a shell (S) domain, hinge (H) region, and protruding (P) domain. The P domain contains the most genetically variable region on the capsid and binding site for histo-blood group antigens (HBGAs). Despite their discovery over 40 years ago, there are still no vaccines or antivirals. In this project we characterized binding of several VHHs (nanobodies) to human norovirus capsid. One nanobody, Nano-85, was broadly reactive, while the others, Nano-25 and Nano-27, were strain specific. All nanobodies bound to the lower region on the P domain and had nanomolar affinities. The Nano-85 binding site mainly comprised highly conserved amino acids among the genetically distinct genogroup II noroviruses. Several of the conserved residues also were recognized by a broadly reactive monoclonal antibody, which suggested this region contained a dominant epitope. Superposition of the P domain nanobody complex structures into a cryoelectron microscopy particle structure revealed that both nanobodies bound at occluded sites on the particles. The flexible hinge region likely permitted a certain degree of P domain movement on the particles in order to accommodate the nanobodies. Interestingly, the Nano-85 binding interaction with intact particles caused the particle disassembly in vitro. Altogether, these results suggested that the highly conserved Nano-85 binding epitope contained a trigger mechanism for particle disassembly.
