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Cambridge Healthtech Institute 第5回

CHO Cell Lines
( CHO細胞株 )

発現、実績、プロセスの強化

2019年1月16日~17日

 

CHO細胞株をテーマにしたこのカンファレンスプログラムでは、細胞株改変、細胞培養、バイオプロセス開発に携わっている研究者や管理職が一堂に会し、タンパク質の発現、製造、製品品質の改善に役立つ最新のデータやツール、戦略などをめぐって議論を展開します。

Final Agenda

1月16日(水)

7:45 am Registration and Morning Coffee

CHO細胞の生産性向上に向けたプロセス開発の成果

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, Chair, Chemical and Biomolecular Engineering, Catherine and Henry Boh Professor of Engineering, Tulane Brain Institute Faculty Member, Tulane 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 Presentation to be Announced

 

9:35 Scaling Up and Scaling Out: Pushing the Boundaries of Transient Protein Production

Ian Wilkinson, PhD, CSO, Research & Development, 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

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


2:00 PLENARY KEYNOTE PANEL

Click here for more details.

PepTalk Perspectives: Point-Counterpoint Discussions

Moderator:
Howard Levine, PhD, President and CEO, BioProcess Technology Consultants






Panelists:
Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck






Lorenz Mayr, PhD, CTO, GE Healthcare Life Sciences




3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

生産性と製品品質の最適化を目的としたCHO細胞の改変

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

7:00 Close of Day

1月17日(木)

7:45 am Registration and Morning Coffee

安定発現CHO細胞株の改良

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

11:00 Manufacturing and Characterization of Novel HIV-1 Vaccine Candidates – Success and Challenges

Antu K. Dey, MSc, PhD, Senior Director, R&D, Vaccine Product Development Center, International AIDS Vaccine Initiative (IAVI)

Discovery endeavors in recent years have identified a number of HIV-1 vaccine candidates that showed promising results in preclinical animal studies. These results have prompted process and analytical development efforts to support cGMP manufacturing of some of these HIV-1 recombinant protein vaccine candidates for evaluation in (proof-of-concept) Phase I clinical studies. To express these recombinant vaccine candidates, stable CHO cell line expression was used. Stable CHO cell line development and clonal selection required a ‘functional’ titer assay for selection of top stable clones. The trimeric complex conformation and extensive posttranslation modifications of these vaccine candidates demanded that extensive characterization of the vaccine antigen produced from top clone be performed to ensure appropriate glycosylation, disulfide linkage and high level of percent trimer. Combination of upstream and downstream process development and subsequent extensive characterization led to production of these vaccine candidates with desired attributes and subsequent ‘release’ of drug product for Phase I clinical evaluation.

11:30 Engineering a Stable CHO Cell Line for the Expression of a MERS-Coronavirus Vaccine Antigen

Mun Peak Nyon, PhD, Research Associate, Pediatrics, Pediatric 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

2:15 Close of CHO Cell Lines Conference

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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