Optimizing Mammalian Cell Lines

 

MEX Header 

Day 1  |  Day 2 

Wednesday, August 26, 2009

7:30am Registration and Morning Coffee

CELL LINE INNOVATIONS

8:20 Chairperson’s Opening Remarks

Susan Sharfstein, Ph.D., Assistant Professor, Chemical and Biological Engineering and Biology, Rensselaer Polytechnic Institute

Opening Keynote Presentation

8:25 Electroporation: Past, Present, and Future

Hunt Potter Huntington Potter, Ph.D., Director, Florida Alzheimer’s Disease Research Center (NIA/NIH); Eric Pfeiffer Chair for Research on Alzheimer’s Disease, USF Pfeiffer Suncoast Alzheimer’s Center and Johnnie B. Byrd Sr. Alzheimer’s Center and Research Institute; Vice President and President Elect of the Faculty, University of South Florida College of Medicine; Member, Moffitt Cancer Center

Today, Electroporation shares only with lipophilic molecules the position of the most used and most efficient method for DNA transfection and is a primary method for delivery of genes into living organisms. For in vivo applications, Electroporation has huge advantages over viral vectors because the inserted gene can be targeted and does not carry in any potentially dangerous viral sequences or proteins of any kind. In future, Electroporation will allow therapeutic gene delivery to be used routinely to correct both inherited defects and the effect of acquired mutations such as cancer.

9:00 Featured Presentation

Strategic Decisions and Risk Assessment in Production Cell Line Development

Susan Dana Jones Susan Dana Jones, Ph.D., Vice President and Senior Consultant, BioProcess Technology Consultants, Inc.

Many different approaches are available to develop high expressing mammalian cell lines for production of therapeutic proteins or antibodies. Decisions on which approach to use will be made based on whether productivity, speed to clinic, suitability for a platform process, or other criteria are the most important. A strategic analysis of different expression technologies, host cell lines, and screening and selection methods for development of high expressing production cell lines will be presented in this talk. Further, an assessment of risks and benefits of different approaches will be discussed.

9:30 Human Cell Systems for the Study of Disease and Therapeutic Development

Dieter-Gruenert--MEX-_WEBDieter C. Gruenert, Ph.D., Senior Scientist & Head, Stem Cell Research Program, California Pacific Medical Center Research Institute; Adjunct Professor, Department of Laboratory Medicine, University of California, San Francisco; Adjunct Professor, Department of Medicine, University of Vermont

The development of human primary and immortalized somatic cell systems as well as the recent development of human embryonic and induced pluripotent stem (hES and iPS, respectively) cell lines has provided a means to study disease pathology and for the development of therapies that can ameliorate that pathology. These cell systems have been crucial in the development of genetic therapies and for high-throughput screening of pharmacological agents. Moreover, the recent advances in hES and iPS cell systems have opened the way for regenerating damaged organs and tissue, and for correcting disease-associated developmental abnormalities.

10:00 Networking Coffee Break with Exhibit and Poster Viewing


OPTIMIZING CELL LINE DEVELOPMENT

10:45 Novel Engineering Strategies for Generating Optimized Mammalian Producer Cell Lines

Lore Florin, Ph.D., Associate Director, Cell Biology, Process Science Biopharmaceuticals, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany

Improved production host cells with improved capacity for protein synthesis and secretion represent the basis for industrial high-titer processes. Here, we report on two cell engineering approaches as part of Boehringer Ingelheim’s high expression platform BI-HEX® which integrates unique vector elements, optimized host cells, efficient screening concepts and chemically-defined media with early assessment of phenotypic stability as well as product characteristics to generate highly productive cell lines of excellent quality.

11:15 Developing Stable Cell Lines for Protein Production

Indresh Srivastava, Ph.D., Associate Director, Vaccines Research, Novartis Vaccines & Diagnostics, Inc.

11:45 Optimization of the CHEF1 Cell Line Development Platform

Howard Clarke, Ph.D., Senior Staff Scientist, Process Development, CMC ICOS Biologics, Inc.

(CHEF1) expression system has been used numerous times to rapidly (~12-16 weeks) create stable CHO cells lines suitable for the manufacture of recombinant therapeutic proteins. We have recently implemented modifications to our cell line development platform including: expression plasmid reconstruction, sterile FACS sorting and screening of high-producing clones, and new host cell development. In comparing these changes to our previous CHEF1 clinical cell line development platform we have improved titer and eliminated animal derived cell culture products without affecting the development timeline.

12:15pm Sponsored Presentation (Opportunity Available – Please contact Suzanne Carroll at scarroll@healthtech.com)

12:30 Lunch on Your Own (Lunch Presentation Opportunity Available) 


OPTIMIZING PRODUCTIVITY

1:55 Chairperson’s Remarks

Dieter C. Gruenert, Ph.D., Senior Scientist & Head, Stem Cell Research Program, California Pacific Medical Center Research Institute; Adjunct Professor, Department of Laboratory Medicine, University of California, San Francisco; Adjunct Professor, Department of Medicine, University of Vermont

2:00 Understanding the Factors that Affect Cell Line Productivity

Susan Sharfstein, Ph.D., Assistant Professor, Chemical and Biological Engineering and Biology, Rensselaer Polytechnic Institute

Current cell line development involves screening of hundreds or even thousands of clones to identify cell lines with good growth and productivity characteristics. This presentation will address some of the fundamental issues that affect cell productivity, including gene copy number, transgene location, and gene accessibility to transcription factors. Using fundamental studies characterizing high productivity cell lines, we hope to provide additional or alternative strategies for cell screening as well as strategies for cellular engineering to more rapidly generate high productivity cell lines.

2:30 Development of a Novel Double Selection System to Improve Antibody Productivity in CHO Cell Lines

Domingos Ng, M.S., Senior Research Associate, Genentech

We have developed a novel selection system in which two selection systems were optimized and combined to establish high productivity cell lines. CHO cell lines generated from this novel double selection system consistently achieve higher titer than those produced from traditional single selection platform. This talk will address the challenges and difficulties we have encountered and overcome in developing this novel double selection system.

3:00 The Application of Transcriptional Profiling for Cell Culture Process Development of a Human-Derived Cell Line

Jui Chang Chuang, Ph.D., Senior Scientist, Cell Culture Process Development, Shire Human Genetic Therapies

A human-derived cell line is utilized at Shire HGT as a platform to manufacture therapeutic glycoproteins. Genome-wide expression profiling was used to analyze the gene expression changes in different production cell lines and process conditions. The application of microarray technology to understand cell culture process development as well as uncover potential cell engineering targets will be discussed.

3:30 Ice Cream Refreshment Break with Exhibit and Poster Viewing


OPTIMIZING TRANSFECTION

4:15 Transient and Stable Transfection Strategies for Expression of Antibodies and Antibody-Like Molecules in Mammalian Cells

Valentina C. Ciccarone, Ph.D., Principal Scientist, Macrogenics, Inc.

The availability of purified, recombinant protein during the research, feasibility, preclinical and clinical phases of biotherapeutic product development is critical to success. In the early stages of research, it is important to be able to express many candidate molecules at the milligram level as rapidly as possible. As the research projects progress to feasibility and product development, the focus shifts to expression of larger batches of fewer molecules. In order to achieve these requirements, we have adapted several strategies. Data will be presented on the expression of humanized antibodies and antibody-like DART molecules at each stage of product development.

4:45 Large-Scale Transfection of 293 and CHO Cells with Polyethylenimine for r-Protein Production
Yves Durocher, Ph.D., Senior Research Officer, Biotechnology Research Institute, Canada
Large-scale transfection of HEK293 cells is a powerful technology for the fast production of r-proteins for preclinical studies. Efforts are also invested in CHO-based transient expression platform in order to provide material more similar to that used later in clinical phases. However, CHO cells usually provide lower levels of transient gene expression compared to 293 cells. We will present our improvements on large-scale transient CHO expression platform using polyethylenimine that allows us to reach r-protein titers closely matching those obtained in 293 cells.

5:15 End of Day

 



For more information, please contact:
Mary Ruberry, Conference Director
Cambridge Healthtech Institute
Phone: 781-972-5421
E-mail: mruberry@healthtech.com

For sponsorship information, please contact:
Suzanne Carroll, Manager, Business Development
Cambridge Healthtech Institute
Phone: 781-972- 5452
E-mail: scarroll@healthtech.com 


By Series:
By Region: