Cambridge Healthtech Institute’s 5th Annual
CHO Cell Lines
Enhancing Expression, Performance, and Process
January 16-17, 2019
CHO cells’ rapid rise in production prominence is due to their adaptability to various culture conditions, gene plasticity, and ability in proper folding, posttranslational modifications, and glycosylation of desired proteins. Thus, advances in
CHO cell lines and culture continue to significantly improve biotherapeutic production. This achievement is due to progress in engineering stable and transient cell lines, enhancing cell culture conditions and performance, as well as optimizing process
development. When all are accomplished, higher-production titers and better product quality result.
Cambridge Healthtech Institute’s CHO Cell Lines conference gathers cell line engineers, cell culture specialists, and bioprocess development managers to explore the latest data, tools, and strategies for improving protein expression, production,
and product quality.
Final Agenda
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WEDNESDAY, JANUARY 16
7:45 am Registration and Morning Coffee (Sapphire West Foyer)
8:15 Chairperson’s Opening Remarks
Jie Zhu, PhD, Associate Director, Cell Culture & Fermentation Sciences, MedImmune
FEATURED PRESENTATION
8:20 Controlling Protein Quality and Antibody Expression
Anne Skaja Robinson, PhD, Head,
Department of Chemical Engineering, Carnegie Mellon University
Monoclonal antibodies (mAbs) are a class of commercially valuable biopharmaceuticals that are used for treating diseases that are typically expressed in mammalian cell lines such as Chinese Hamster Ovary (CHO) cells to enable posttranslational modifications.
One such posttranslational modification that results in structural and pharmacological changes in the protein is N-linked glycosylation. This talk addresses approaches to maintaining desired product quality of mAbs in the presence of process variations
during manufacturing.
8:50 Therapeutic Antibody Fragments: Simplifying the Choice of the Expression Platform and Optimizing Protein L Capture
Philippe Billiald, PharmD, PhD, Professor, Biochemistry,
University of Paris-Sud; Co-Founder, Acticor Biotech
Therapeutic antibody fragments are produced from various hosts, but no downstream process is well established. Here, we report a universal method to confer Protein L binding ability to any antibody fragment. In addition, based on a case study, we assess
E. coli, P. pastoris and CHO expression systems in terms of cell line development, culture time, product quality and cost. We report differences to consider before pharmaceutical
development and moving forward to the clinic.
9:20 Overcoming the Key Bottlenecks in Cell Line Development: Increasing Titers and Streamlining Cell Line Development
Fay Saunders, Head of Upstream Mammalian Development, Mammalian Cell Culture, FUJIFILM Diosynth Biotechnologies
9:35 NEW: Scaling Up and Scaling Out: Pushing the Boundaries of Transient Protein Production
Michael Fiebig, PhD, Director, Products and Innovations, Absolute Antibody Ltd
Whilst transient yields have improved drastically in the last decade, scalable systems are time-consuming and costly to implement. Absolute Antibody has developed systems which scale up and scale out protein expression and purification, enabling the rapid
and cost-effective production of milligram-to-gram quantities of large panels of proteins.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
10:35 Multi-Specificity of a Recombinant Monoclonal Antibody
Gary McLean, PhD, Reader in Molecular
Immunology, Cellular and Molecular Immunology Research Centre, London Metropolitan University; Honorary Senior Research Fellow, National Heart and Lung Institute, Imperial College London
Whilst studying the cellular molecular switch protein m-ras, a recombinant monoclonal antibody was generated to an m-ras-specific peptide sequence. The recombinant antibody was expressed in mammalian cells and interestingly the IgG bound to both recombinant
full-length m-ras and h-ras proteins. The cross-reactive binding of the monoclonal Ab to h-ras revealed that the Ab showed preference for peptide sequences containing multiple positively charged amino acid residues. These data reinforce the concept
of antibody multi-specificity through multiple interactions of the Ab paratope with diverse polypeptides and emphasize the importance of immunogen and Ab selection processes when generating recombinant monoclonal Abs.
11:05 Mammalian Display Platform for Facile, FACS-Based Engineering of Antibodies and Other Receptors
Jennifer Maynard, PhD,
Associate Professor, Chemical Engineering, University of Texas at Austin
Discovery of new antibodies is most commonly performed using phage or yeast display, but mammalian cells are used for large-scale production because of the complex antibody structure, including multiple disulfide bonds and a key glycosylation required
for function. To circumvent problems associated with changing hosts, we developed a screening platform on CHO cells which allows for antibody selection in the same host used for manufacturing. We have used this approach to affinity mature an antibody
Fab, a human T cell receptor and modulate binding of human IgG1 Fc to the FcgRIIIa receptor. Finally, modifications of the approach allow us to select for receptors that activate T cells in the presence of ligand as opposed to just binding the ligand.
11:35 Understanding and Engineering Fc Glycans in CHO Cells for the Production of Therapeutic Proteins
Jie Zhu, PhD, Associate Director, Cell Culture
& Fermentation Sciences, MedImmune
Glycosylation of monoclonal antibody and derivatives plays an important role for complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) functions. Case studies are presented here on the generation of stable CHO
cells cell line to produce recombinant proteins with desirable and consistent glycosylation patterns in Fc domain using both vector and host engineering approaches.
12:05 pm Session Break
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
PLENARY KEYNOTE PANEL (Aqua Salon)
Click here for more details.
PepTalk Perspectives: Point-Counterpoint Discussions
2:00 Plenary Keynote Introduction
Norman Packard, PhD, CEO, Daptics
2:10 Plenary Keynote Panel
Moderator:
Howard Levine, PhD, President and CEO, BioProcess Technology Consultants
Panelists:
George Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG
Manon Cox, PhD, Co-Founder & CEO, NextWaveBio
Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck
Paul Jorjorian, Vice President, BioProcess Sciences, Thermo Fisher Scientific
Marina Kirkitadze, PhD, Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada
Stefan R. Schmidt, PhD, MBA, Head, Operations (COO), BioAtrium AG
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
4:00 Chairperson’s Remarks
Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark
4:05 Implementing Next-Generation Sequencing for DNA-Based Sequence Variant Analysis of Recombinant Proteins
Ulrich Goepfert, PhD, Principal
Scientist, Large Molecule Research, Roche Pharma Research & Early Development, Roche Innovation Center Munich
Sequence variants are unintended amino acid substitutions in biopharmaceuticals, which can either be due to the manufacturing process or mutations of the transgene. Transgene mutations are permanent properties of affected cell lines and may give rise
to critical quality attributes. Therefore, mutated cell lines need to be identified and excluded from development. We share our experience with Next-Generation Sequencing as an efficient and highly sensitive method to detect DNA-based sequence variants.
4:35 The BEST of Both Worlds – Targeted Integration and Multiple Copies: How Can These Go Together for Improved Cell Line Development?
Anton Bauer, PhD, MBA, COO, R&D,
The Antibody Lab GmbH
Targeted Hot Spot integration and multiplication of independent expression units – can this go together and even speed up cell line development? Targeted integration of the gene-of-interest in an expression hot spot is contributing to high protein
expression yields as well as to epigenetic stability of selected clones. This increases the probability of identifying promising clones and lowers the attrition rate during process development. By targeting the Rosa26 Hot Spot in vitro we
generated BAC-based expression vectors, which integrated in multiple copies into the CHO host cell chromatin and acted as independent expression units. This allowed us to adapt the selection process and developed long-term stable high-yield production
cell lines at an unprecedented speed. New data from case studies and further improved vector versions demonstrate the capability of the technology.
5:05 Optimizing Productivity and Product Quality of Difficult-to-Express Biosimilars with a Novel NS0 Platform
Darryl Sampey, PhD, President
& CEO, Research & Development, BioFactura, Inc.
Biosimilar cell lines that produce complex glycoproteins such as monoclonal antibodies must be both highly productive and express a product with critical quality attributes closely matching those of the innovator references. In this presentation, a novel
biomanufacturing platform and case studies are described that harness the commercially established NS0 host cell in new ways to create stable, productive cell lines with product characteristics meeting biosimilar technical and regulatory demands.
5:35 Engineering CHO Cell Lines for the Production of Hard-to-Produce Proteins
Bjørn Voldborg, MSc,
Director, CHO Cell Line Development, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark
Using our high-throughput cell line engineering platform, we have engineered CHO cells able to produce a therapeutic protein that has previously not been possible to produce in CHO cells. This approach may result in improved therapeutic proteins, with
better biological properties, such as increased half-life, improved activity, etc.
6:05 - 7:00 Networking Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:00 Close of Day
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THURSDAY, JANUARY 17
7:45 am Registration and Morning Coffee (Sapphire West Foyer)
8:10 Organizer’s Remarks
Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute
8:15 Chairperson’s Remarks
Howard R.G. Clarke, PhD, Principal Scientist, Cell Sciences, Seattle Genetics
KEYNOTE PRESENTATION
8:20 Chromosome Stability Approach: Lengthening of High-Yield Production Levels of IgG-Producing CHO Cells by Downregulation
of Breast Cancer 1
Takeshi Omasa, PhD, Professor, Department of Material and Life Science, Graduate School of Engineering, Osaka University
The effects of breast cancer 1 (BRCA1) downregulation on gene amplification efficiency and long-term productivity were investigated in CHO cells. Our results suggest that high-producing cells, which maintain their productivity long term, were efficiently
established by BRCA1 downregulation. In this presentation, I would like to introduce the chromosome stability and effect of BRCA1 downregulation.
9:00 Antibody Expression Stability in CHO Clonally Derived Cell Lines and Their Subclones
Howard R.G. Clarke, PhD, Principal
Scientist, Cell Sciences, Seattle Genetics
Cell line development involves lengthy screening to identify a stable line having consistent growth, productivity and product quality. To investigate production stability in CHO cells, we analyzed primary clones and their respective subclones. Cell lines
derived from single cell progenitors grow into populations of cells with phenotypic heterogeneity. Here I present the genetic and epigenetic characterization of these heterogeneous cell line populations.
9:30 Presentation to be Announced
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 NEW: SELECTED POSTER PRESENTATION: Implementing an Automated Platform for Cell Line Development
Xiaoyan Tang, MD, Senior Scientist, Cell Line Development, Merck Research Labs
11:30 Engineering a Stable CHO Cell Line for the Expression of a MERS-Coronavirus Vaccine Antigen
Wen-Hsiang Chen, PhD, Assistant Professor, Department of Pediatric, Section of Tropical Medicine, Baylor College of Medicine
Human vaccine against MERS-CoV is not available. We have developed a stably transfected adherent CHO cell line for the production of the MERS-CoV protein subunit, S377-588 (Fc tagged). The adjuvanted protein vaccine expressed in adherent CHO could protect
transgenic animal model from infection with live MERS-CoV. We also have developed a suspension monoclonal CHO cell line able to express S377-588-Fc in serum-free media, which is ready for scaled-up production.
12:00 pm Session Break
12:10 Luncheon Presentation: New Tools for Screening & Harvesting Solutions for CHO & HEK293 Cells, for Both Transient and Stable Cells
Samuel Ellis, Vice President,
Thomson Instrument Company
Evaluation of different transfection tools, product quality, and titer for both CHO and HEK293 cell lines. Data will be presented on techniques and technology that mimic large-scale bioreactors in non-controlled devices from 1mL-3L. Technologies presented
include well plates and culture tube systems with incorporated filtration methodology. A new direct harvesting technique will also be introduced that eliminates centrifugation while maintaining 0.2um sterile filtration. All of these tools will be
presented with case studies from scientists.
12:40 Luncheon Presentation II (Sponsorship Opportunity Available)
1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
2:15 Close of CHO Cell Lines Conference
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