Cambridge Healthtech Instituteの第5回年次会議

Cell Line Development
(細胞株開発)

堅牢な細胞株のエンジニアリングに対する新しい技術、ビッグデータソリューション、ベストプラクティス

2023年3月15 - 16日、CET(中部欧州標準時)

バイオ医薬品分野がますます複雑になるにつれ、細胞株のエンジニアリングは、依然としてバイオ医薬品開発の基礎ステップです。この基礎により、新興の研究と画期的な戦略で、プロジェクトの目標を迅速かつ安価に達成する細胞株が実現されます。第5回「細胞株開発」年次会議では、細胞エンジニアリング、新興モダリティのエンジニアリング、新しい技術、上流工程プロセスのこの段階へのモデリングと機械学習の統合に関し、専門家が共有する戦略やベストプラクティスを紹介します。

3月15日(水)

Registration Open10:30

PLENARY SESSION: EMERGING MODALITIES, PLATFORMS, AND TECHNOLOGIES - FROM mRNA TO PROTEINS
基調講演:新興のモダリティ、プラットフォーム、技術 - mRNAからタンパク質へ

11:15

Chairperson's Opening Remarks

Margit Holzer, PhD, Owner, Ulysse Consult

11:20 PLENARY PRESENTATION:

Overcoming CMC and Supply Chain Challenges for mRNA Technologies

Gregory Troiano, Chief Manufacturing Officer, mRNA Center of Excellence, sanofi

Thanks to the rapid development of mRNA vaccines for COVID-19, the industry now has the momentum and resources to overcome many of the early CMC challenges and realize its enormous potential. This presentation will discuss the strategies in place to overcome CMC and supply chain challenges for mRNA technologies already and future innovations primed to take it to the next level.

11:50 PLENARY PRESENTATION:

Affinity Proteins for Biotechnological and Medical Purposes

Sophia Hober, PhD, Professor, School of Biotechnology, KTH Royal Institute of Technology

Affinity proteins are crucial for life, for building structures, performing reactions, and for signaling purposes. In life sciences and medicine, affinity proteins are used to generate knowledge, but also for diagnostic and therapeutic purposes. This talk will cover how antibodies and small affinity molecules can be used to map the human proteome, develop diagnostic tools for in vivo visualization as well as efficiently purify therapeutics based on antibodies.

Transition to Sessions12:20

12:30 Designing Purification Strategies for Bispecific Antibodies Based on Molecule Design

Jakob Liderfelt, Global Product Manager - Antibody Polishing, Cytiva

Developing purification protocols for multispecific antibodies present extra challenges compared to conventional therapeutic monoclonal antibodies (mAbs). Strategies for efficient capture and polishing are discussed already in antibody engineering. Strategies include available resins and methods and need to give sufficient separation of product and process related impurities. This presentation covers different aspects of designing a GMP purification process for bispecific antibodies.

Networking Lunch (Sponsor Opportunity Available)13:00

CELL ENGINEERING
細胞エンジニアリング

14:00

Chairperson’s Remarks

Arnaud Poterszman, PhD, Research Director, Integrated Structural Biology, IGBMC, France

14:05

Understanding Recombinant Protein Production at Single Cell Resolution

Colin Clark, PhD, Principal Investigator, NIBRT; Associate Professor University College Dublin, Ireland

Single cell omics is a powerful technology for the understanding of biological systems. In this talk, studies from our laboratory focused on capturing chromatin accessibility, gene expression ,and protein abundance from monoclonal antibody CHO cell lines will be presented. Single cell omics platforms and computational approaches for data analysis will also be discussed.

14:35

Modification of Lipid Metabolism in Chinese Hamster Ovary Cells for Enhanced Recombinant Protein Production

James Budge, PhD, Postdoctoral Researcher, Industrial Biotechnology, University of Kent, United Kingdom

Lipid metabolism plays a key role in cellular processes that are central to achieving high recombinant protein titres. Processes such as secretion, cell division, and endoplasmic reticulum size and function are highly dependent on lipids and their metabolism. In this approach, we have used genetic engineering techniques to optimise lipid metabolism in CHOK1-SV cells which has been successful in expanding the endoplasmic reticulum and ultimately enhancing recombinant protein titres between 1.5 and 9-fold.

15:05

KEYNOTE PRESENTATION: A Cell Engineer's Perspective on Platform Technology for the Production of Therapeutic Proteins

Gyun Min Lee, PhD, Professor, Cell and Developmental Biology, KAIST, Korea

Biotech companies have their own platform technologies for the efficient production of therapeutic proteins. The superiority of a platform is determined by its ability to rapidly produce large quantities of high-quality therapeutic proteins. A next generation platform employs CHO host cells engineered to overcome bottlenecks and negative effects on productivity and CRISPR/Cas9-mediated targeted integration combined with recombinase-mediated cassette exchange for rapid cell line generation.

15:35 Talk Title to be Announced

Speaker to be Announced

Refreshment Break in the Exhibit Hall with Poster Viewing16:05

16:40

Top-Down Strategies for the Preparation and Characterization of Human Macromolecular Assemblies: Insights from Genome Editing Approaches

Arnaud Poterszman, PhD, Research Director, Integrated Structural Biology, IGBMC, France

Macromolecular complexes are cornerstones of most, if not all, biological processes in cells. We will illustrate how the CrispR/Cas9 editing technology can be used for gene tagging in order to introduce affinity tags and facilitate the purification of proteins/macromolecular assemblies expressed in physiological conditions. We will also discuss tagging proteins with fluorescent reporters in view of imaging and functional proteomics applications.

17:10

Development of an Inducible rAAV-Producer Cell Line

Sofia Zaichick, PhD, Lead Researcher, Gene Therapy Program, Pathology and Laboratory Medicine, University of Pennsylvania, USA

There is a need for a better and more cost-effective method for rAAV production to meet the high demand in the gene therapy field. We address this issue by creating an inducible rAAV producer HEK293 cell line that does not need further transient transfection with plasmid DNA or infection with a helper virus.

17:40 Accelerating Clone Selection & Upstream Process Development Through Data Driven Decisions

Ben Wilkes, Principal Biopharma Market Development Manager, Waters Corporation

Bioprocess scientists aim at optimizing biotherapeutics manufacturing processes to maximize drug product quality, yield, and manufacturing efficiency. Currently, information on product and media attributes required for informed decision-making is not readily available: the results are generally lagging several weeks behind sampling. Direct measurement of CQAs and CCM has recently been offered thanks to dedicated workflows coupling small bioreactors like the Sartorius Ambr systems to the Waters BioAccord LC-MS system.

Close of Day18:15

3月16日(木)

Registration and Morning Coffee08:00

OPTIMISING CELL LINE DEVELOPMENT
細胞株開発の最適化

08:25

Chairperson’s Remarks

Philip Probert, PhD, Technology Lead, CPI, United Kingdom

08:30

Accelerated Cell Line Engineering Using Multiplexed, Targeted Integration

Lars Keld Nielsen, PhD, Scientific Director, Novo Nordisk Foundation Center for Biosustainability, DTU, Denmark

The complexity of new biopharma products together with the need for precise PTMs (e.g., blood factors or bio-similars) is challenging for conventional strain engineering strategies. The availability of the CHO and Chinese Hamster genomes together with advances in mammalian genome editing has renewed interest in using systems and synthetic biology to guide rational strain design. In this talk, we will present recent work on model-based design strategies, efficient multigene genome editing, as well as multi-omics characterization. We will highlight outstanding challenges that need to be resolved before a CHO Biofoundry can be fully realized.

09:00

Cell Line Development in Biologics Discovery and Development

Bernd Voedisch, PhD, Principal Scientist II, Novartis Pharma AG, Switzerland

The presentation will highlight the components of the cell systems employed for generations of research cell lines and CHO manufacturing cell lines, and recent developments aiming at enhancing the quality and titer of produced complex biotherapeutic proteins.

09:30

Leveraging a Transposase-Mediated Semi-Targeted Transgene Integration System to Enable WARP Speed Development of a Monoclonal Antibody

Nikolas Zeh, PhD, Postdoctoral Researcher, Cell Biology, Cell Line Development, Bioprocess Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany

Cell line development (CLD) represents a central part of a biologics development process. Hence, accelerating the CLD process would have substantial impact on overall timelines. Integration of the semi-targeted integration (STI) technology into our CLD platform enabled manufacturing of a therapeutic antibody at 2,000L scale in less than 3 months. Next, by using a clonally derived production cell line, a process with ~5g/L was implemented in less than 9 months.

10:00 Talk Title to be Announced

Speaker to be Announced

10:15 Application of Efficient sStrategies for the dDevelopment of More Complex BIotherapeutics

Fay Saunders, PhD, Director of Mammalian Cell Culture Process Development, FUJIFILM Diosynth Biotechnologies

The Apollo™X expression system and associated technologies provide versatile solutions that are compatible with a diverse range of biotherapeutics such as Bispecific and Fc-fusion molecules. We demonstrate that the system has the ability to express these proteins efficiently. The inherent complexity of these molecules means that product quality assessments during development can be challenging. FUJIFILM Diosynth Biotechnologies has developed methods to support this analysis which allows a streamlined development process.

Coffee Break in the Exhibit Hall with Poster Viewing10:30

11:00

New CHO Host Cell Line: Genetic Reporter for Fast Productivity Assessment

Katarzyna Sobkowiak, PhD, Scientist, Biopharma, Merck Serono SA, Switzerland

Chinese hamster ovary cells are commonly used for therapeutic proteins production. Major challenge of cell line development is to obtain stable high-producing clones. Therefore, we set out to develop new CHO host cell line that would be selected based on the growth characteristics as well as productivity and secretion potential. To assess cell productivity and secretion capabilities, we used genetic reporter that allowed us for high-throughput screen of CHO cells.

11:30

Anticipated Cell Line Selection in Biopharmaceutical Process Development through Machine Learning on Metabolomics and Process Dynamics

Pierantonio Facco, PhD, Associate Professor, University of Padova, Italy

In this presentation, it will be shown how machine learning can exploit the dynamic information on metabolomic and process data to support the selection of highly productive cell lines during bioprocess development and scale-up. In this way, high productive cell lines and the biomarkers that are most related to cell productivity are identified already at the early stages of experimentation.

12:00

Strategies for Fast Cell Line Development

Stefan Wieschalka, Scientist, Early Stage Bioprocess Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany

In-licensing of new molecules may come along with unforeseen CMC challenges. In the case study at hand, we observed significant product fragmentation using a producer cell line from an in-licensing partner. To ensure clinical supply and gain a scientific understanding, potential root causes and solutions were investigated, including the fast generation of a new producer cell line. The exploitation of transposase-mediated semi-targeted transgene integration facilitated the identification of stable producer pools free of fragmentation in a competitive project timeline. Thus, fast cell line development can tackle CMC difficulties, without stretching project timelines.

12:30 Go beyond Titer and Select Top Producers with Favorable Quality Attributes within 5 Days of Cloning

Speaker to be Announced, Berkeley Lights

Despite a growing need for earlier information on quality and manufacturability, initial clone screening in mammalian CLD continues to focus on selection for growth and titer. Yet the fastest-growing and highest-producing clones may not secrete a product with the appropriate quality attributes. The Berkeley Lights Opto CLD workflow accelerates early CLD by integrating high throughput cell sorting, cloning, culture, productivity, growth, and product quality assays into a single, five-day automated process.

Networking Lunch (Sponsor Opportunity Available)13:00

13:45

Chairperson’s Remarks

Pierantonio Facco, PhD, Associate Professor, University of Padova, Italy

13:50

Systems and Synthetic Biology to Define Limiting Genes and Tune Their Expression

Johan Rockberg, PhD, Professor, Antibody Technology and Directed Evolution, KTH Royal Institute of Technology, Sweden

Biopharmaceutical and AAV production in CHO/HEK293 challenges their translational, secretional, and metabolic boundaries. We show the importance of ER-mitochondria signaling to fulfill energy demand of secreted products. Further, we exemplify how systems and synthetic biology can be used to define limiting genes and tune their expression improving activity of therapeutic enzymes 100-fold by OMICS and engineered TIS and regulatory elements for precise expression.

CELL-FREE SYNTHESIS
無細胞合成

14:20

Development of a Manufacturing Platform with Analytical Toolkit for mRNA-Based Products

Philip Probert, PhD, Technology Lead, CPI, United Kingdom

mRNA based products represent a novel emerging modality with the potential to treat the previously untreatable. This talk will outline and present case data on the development of a flexible and scalable manufacturing process for mRNA-LNP products. This will include the development of the analytical toolkit to support process development and manufacture, which encompasses biochemical, structural and biological activity assays for product characterisation.

14:50

FEATURED PRESENTATION: Cell-Free Protein Synthesis of Virus-Like Particles

Daniel G. Bracewell, PhD, Professor, Bioprocess Analysis, Biochemical Engineering, University College London, United Kingdom

Virus-like particles (VLPs) have proven potent vaccines. However, their complex self-assembly can make their development challenging. Here we describe progress in the use of E. coli cell-free synthesis platforms to expedite these activities for this product class. Two examples will be given: picornavirus-like particle vaccine candidates stabilized by N-myristoylation and universal influenza vaccine candidates based on tandem-core hepatitis B core antigen VLPs.

Close of Summit15:20

* 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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Prelim Agenda Now Available

3月14 - 15日

CELL CULTURE AND BIOPRODUCTION

ADVANCES IN RECOVERY & PURIFICATION

GENE THERAPY CMC AND ANALYTICS

CELL THERAPY MANUFACTURING

ANALYTICS AND CHARACTERIZATION

3月14 - 15日

CELL LINE DEVELOPMENT

INTENSIFIED & CONTINUOUS PROCESSING

GENE THERAPY MANUFACTURING

CELL THERAPY CMC AND ANALYTICS

FORMULATION AND STABILITY