Cambridge Healthtech Institute’s 8th Annual
Optimizing Cell Line Development
Part of CHI's 8th Annual The Bioprocessing Summit
August 18-19, 2016 | Westin Boston Waterfront | Boston, Massachusetts
The “Optimizing Cell Line Development” meeting brings together experts in cell line development and protein expression who share their real-world strategies for achieving cell lines that meet bottom-line goals faster and at lower expense.
Their practical and detailed insights will illustrate how to best optimize codons, construct vectors, and how to select and engineer clones and host systems. Gaining a greater understanding of cells through sequencing and the omics sciences will also
be addressed, including the CHO genome research, metabolomics, assays, and QPCR. In addition, challenges for introducing new technologies, such as in silico modeling, will be discussed, along with an overview of industrial trends and regulatory perspectives.
Thursday, August 18
11:30 am Registration Opens
12:15 pm Lunch Available for Purchase in the Exhibit Hall
1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Opening Remarks
Nathan E. Lewis, Ph.D., Assistant Professor, Department of Pediatrics, University of California, San Diego
2:00 KEYNOTE PRESENTATION:
Tilting at Windmills: Cell Line Development Impacts on Quality, Time and Costs
Steven Lang, Ph.D., M.B.A., Director, Early Stage Cell Culture, Genentech, Inc., a member of the Roche
Advances in technology and processes have made significant improvements in cell line development efficiency. However, the continued pressure to reduce timelines and costs while delivering on quality has created imaginary giants. This talk will
discuss cell line development challenges and how focusing on real issues can improve the value of clinical programs.
2:45 Technology Toolbox for Cell Line Development – Next-Generation Cell Line Development Technologies
Holger Laux, Ph.D., Fellow, Novartis
A novel toolbox of vector elements and novel engineered CHO cell lines were developed which results in significant increase of titer and improved product quality. We have evaluated novel vector elements with a variety of antibody projects resulting
in an increase of titer. Especially the combination of the recently published CHO genome in combination with screening methods and cell line engineering tools has enabled the development of a superior CHO cell.
3:15 What is Your Cell Line Really Translating? Enhancing Protein Production with Ribosomal Profiling and Systems Biology Analysis
Nathan E. Lewis, Ph.D., Assistant Professor, Department of Pediatrics, University of California, San
Mammalian cells channel their resources to produce recombinant protein drugs, but it is unclear how recombinant genes impact global translation and if they are translated as efficiently as host genes. To answer these questions, we gained a global
view of mRNA translation in IgG-producing CHO cells using ribosomal profiling. We demonstrate how these data can be harnessed to guide cell line development for protein production.
3:45 Refreshment Break
4:15 A Novel Platform for High Throughput Cell Line Screening & Development
Christoph Freiberg, Ph.D., Senior Scientific Consultant, Biologics, Genedata
Co-developed with leading biopharmaceutical companies, we have implemented a dedicated cell line development platform for fully automating the clone line selection and assessment process to increase process efficiency and quality. It supports the
entire cell line development workflow including seeding, selection, incubation, passaging, analyzing, and cryo-conservation and tracks the full history of all clones along with product quality and analytics data. It directly integrates with instruments,
such as pipetting robots, colony pickers, and bioanalyzers.
4:45 Quality Attributes are Critical for the Lead Clone Selection and CHO Cell Culture Process Development: A Case Study
Jianlin (Jim) Xu, Ph.D., Principle Scientist, Bristol-Myers Squibb Company
5:15 End of Day
5:15 Registration for Dinner Short Courses
6:00 – 8:30 Recommended Dinner Short Course*
SC11: Regulatory and Scientific Base of Monoclonality for Generating Protein Expression Cell Banks
* Separate registration required
Friday, August 19
8:00 am Registration Opens and Morning Coffee
8:25 Chairperson’s Remarks
Susan Sharfstein, Ph.D., Associate Professor, Nanobioscience, Nanoscale Science and Engineering, SUNY Polytechnic Institute
8:30 Accelerated Genome Engineering of CHO Cell Factories for Improved Protein Production
Helene Faustrup Kildegaard, Ph.D., Senior Researcher and Co-Principal Investigator,
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark
Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical industry as a host for the production of complex pharmaceutical proteins. Thus, accelerated genome engineering of CHO cell factories to improve product yield and quality is
of great interest. Here, our recent efforts in generating desirable CHO cell factories with predicted performance using genome engineering, systems biology data and high-throughput screening, will be presented.
9:00 Cell Line Development: Glycoengineering of Chinese Hamster Ovary Cells for Improving Biotherapeutics’ Efficacies
Andrew Chengyu Chung, MSE, Researcher, Chemical and Biomolecular Engineering,
Johns Hopkins University
Many biotherapeutics include post-translational modifications such as glycosylation. The chemical composition of these glycans can influence drug effectiveness. Sialylation is one of the most important glycan modifications due to its negative charge
and terminal location. In this study, we applied genetic engineering strategies to modulate the level of sialylation content on various potential biotherapeutics.
9:30 Epigenetic Effects on Antibody Production in CHO Cells
Susan Sharfstein, Ph.D., Associate Professor, Nanobioscience, Nanoscale Science and Engineering,
SUNY Polytechnic Institute
Identifying characteristics of high productivity cell clones is critical for rapid cell line development. We evaluated epigenetic differences between parental clones and DHFR-amplified progeny including transcription factor activation and DNA methylation.
These studies suggest that transcription factor binding is altered in different families of parental cell lines and progeny, providing possible strategies for cell line engineering.
10:00 Networking Coffee Break
10:30 Know Thy Cells: Improving Biomedical Research Reproducibility
Leonard P. Freedman, Ph.D., President, Global Biological Standards Institute
Sources of irreproducibility are often magnified by the explosion of high-throughput technologies, genomics, and other data-intensive disciplines. This presentation will use examples of biological materials and reagents, specifically cell lines and
antibodies, on the impact of irreproducibility in basic/preclinical research and development, and how the implementation of consensus-based standards to authenticate and certify these reagents will lead to both increased rates of reproducibility
and dramatic returns on research funding investments.
11:00 Cell Line and Biospecimen Authentication: Challenges and Solutions for Biomedical Science
Richard M. Neve, Ph.D., Senior Research Scientist I, Gilead Sciences, Inc.
The use of cell lines and biosamples are widespread in biomedical research. Contamination of stocks and confusion of cell line/sample origin frequently occur, resulting in wasted research funds and delaying development of important medicines for patients.
This presentation outlines solutions for these issues by defining a framework of quality controls and best practices to prevent and detect the most common forms of cross-contamination.
11:30 Authentication of Mouse, CHO, and Rat Cell Lines
Jamie Almeida, Microbiologist, Biochemical Science Division, Bioassay Methods Group, NIST
Cell line authentication has never been more necessary in the current environment. Currently, there are no standards for cell line authentication for nonhuman cell lines. We have developed rapid, sensitive, and specific multiplex PCR assays targeting
short tandem repeat markers for mouse and Chinese hamster cell lines, and we have identified STR markers specific to rat. Use of these assays provide assurance in cell line identity for the validation of downstream products.
12:00 pm Sponsored Presentations (Opportunities Available)
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:15 Session Break
1:25 Chairperson’s Remarks
Christoph Freiberg, Ph.D., Senior Scientific Consultant, Biologics, Genedata
1:30 Greater Predictability in Establishing Optimal Biologic Production Systems Using Integrated Synthetic Biology Approaches
Ian Fotheringham, Ph.D., Managing Director, Ingenza, Ltd.
In this talk, I will describe how Ingenza develops and applies various synthetic biology tools to enable us to more predictably achieve efficient, soluble and stable expression of active biologics using both mammalian cell lines and microbial
strains. I will describe scaled commercial examples that solved customer problems and illustrate the utility of our approach.
2:00 Switchable Membrane Reporter (SwiMR) Technology for Facile Cell Line Development
Bo Yu, Ph.D., Co-Founder & CSO, Larix Bioscience
Switchable Membrane Reporter (SwiMR) technology is the most efficient technology available today for the isolation of production cell lines. It utilizes a unique switchable reporter system to facilitate FACS-based enrichment and isolation of high
producing cells. This eliminates the requirement for gene amplification and reduces cell line screening time from 4-8 months to 2-3 months. The SwiMR technology has been used to generate production CHO cells for multiple antibodies.
2:30 Genetic Glycoengeneering for Improvement of Biopharmaceuticals
Steffen Kreye, M.S., Scientist, USP Development, Glycotope GmbH
Glycotope’s GEX™ platform comprises a comprehensive portfolio of proprietary glycoengineered human suspension cell lines. Gene editing technologies like CRISPR/Cas9 are very efficient tools to further gear up the glycosylation machinery for the specific needs of human biopharmaceuticals.
Besides the sialylation degree, the amount of terminal GalNAc on the glycans greatly impacts the pharmacokinetic parameters of glycoproteins. By using CRISPR/Cas9, we efficiently knocked out the respective transferases. FactorVII expressed in these cells showed unexpected changes in other N-glycan features leading to a recombinant FVII molecule that resembled the human plasma derived FVII to a high extent.
3:00 Close of Conference