The Bioprocessing Summit
2013 Archived Content

August 21-22, 2013

Cambridge Healthtech Institute’s 5th Annual
Optimizing Cell Line Development

Enhancing Expression


Day 1 | Day 2 | Short Courses | Download Brochure 

Wednesday, August 21

7:45 am Registration & Morning Coffee


Cell Line Development 

8:15 Chairperson’s Remarks

Arnaud Poterszman, Ph.D., Research Director, Integrated Structural Biology, Institute de Génétique, et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS


8:20 Opening Keynote Presentation:

Achievements, Challenges and Future of the Manufacture of Pharmaceutical Proteins with Animal Cells in Bioreactors

Florian-WurmFlorian M. Wurm, Ph.D., Professor, Chemistry Engineering & Cell Bio Lab, School of Life Sciences, Integrative Bioscience Institute, École Polytechnique Federale De Lausanne (EPFL), and Founder & CSO, ExcellGene SA - Biography 

The g/L yield range for CHO-derived proteins has become standard today. Higher yield is no longer a true goal for today’s development teams. However, more robust and more predictable processes, executed under reduced timeframes and established at a lower cost is essential, since an ever larger number of product candidates will require at least phase I/II evaluations. This talk will highlight key developments and will also give a view on the future of manufacturing in this field.

9:00 Featured Presentation:

Rapid Generation of Stable CHO Pools and Clones

Yves-DurocherYves Durocher, Ph.D., Senior Research Officer, Biotechnology Research Institute, National Research Council Canada - Biography 

We will present data describing our new platform that allows the generation of stable CHO pools capable of producing up to 700 mg/L of monoclonal antibodies (Mab) in less than 30 days post-transfection. We believe that this platform is a viable alternative to large-scale CHO transfection when multi-gram quantities of r-protein candidates are needed for therapeutics development. As clones producing g/L quantities of Mab can be rapidly isolated from the pools, this also makes our platform very attractive for the manufacturing of biologics.

9:30 Case Study: Fast Cell Line and Process Development to Produce a Complex Novel IL2-Based Immunocytokine in High Quality

Ingo-GorrIngo Gorr, Ph.D., Senior Scientist, Cell Culture Research, F. Hoffmann-La Roche - Biography 

In this case study a fast but elegant strategy for cell line selection and development of a manufacturing process for a novel IL2-based immunocytokine for cancer therapy is presented. Here, only CLD, USP and DSP together are capable of reducing critical impurities. Intriguing strategies to achieve a high quality therapeutic protein in combination with accelerated timelines are highlighted.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

Delphi Genetics10:45 The Use of Bacterial Poison-Antidote Module for Efficient Antibiotic-Free Bioproduction in E. coli 

Benjamin Michel, Ph.D., Project Manager, Delphi Genetics SA 

Delphi Genetics develops technologies which enable bioproduction without using antibiotics in line with the regulatory guidance (FDA, USDA and EMA). Moreover, these technologies permit an increase of yield (protein or pDNA) by avoiding a burden of energy due to expression of antibiotic resistance gene.

11:15 Optimizing Cell Line Development for Expression of Bispecific DART molecules:  Case Studies

Valentina-CiccaroneValentina Ciccarone, Ph.D., Principal Scientist, MacroGenics, Inc. - Biography 

Dual Affinity Re-Targeting (DART) proteins are antibody-like therapeutic proteins that can target multiple different epitopes. These molecules have excellent product stability, optimal chain pairing, predictable antigen-recognition, and enhanced half-life in vivo.  Several protein and cell line engineering strategies have been incorporated to achieve correct molecule assembly, high expression levels, and biological activity of these complex, multi-chain proteins.  Data will be presented from case studies for the expression of two DART proteins with different structures and target specificities.
 

 

Selexis11:45 A CHO-M Cell Combinatorial Library for the Improved Selection of Recombinant Protein Production Clones

Pierre-Alain GirodPierre-Alain Girod, Ph.D., CSO, Selexis 

With some proteins, optimal productivity requires more than elevated transcription. Metabolic limitations, trafficking backlogs, improper folding and altered post-translational modifications can all effect output. Utilizing the CHO-M genome and transcriptome, we have engineered a combinatorial CHO cell library to address a broad range of these production bottlenecks.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


CHO Cell Line Optimization 

1:55 Chairperson’s Remarks

Valentina Ciccarone, Ph.D., Principal Scientist, MacroGenics, Inc. - Biography 

2:00 Impact of miR-7 Over-Expression on the Proteome of Chinese Hamster Ovary Cells

Paula-MeleadyPaula Meleady, Ph.D., Senior Research Scientist and Programme Leader, National Institute for Cellular Biotechnology, Dublin City University - Biography 

MicroRNAs play critical roles in the regulation of biological processes thus representing potential engineering routes towards enhancing desirable characteristics of mammalian cells for biopharmaceutical production. We have carried out quantitative label-free LC-MS/MS proteomic analysis of CHO cells following over-expression of miR-7, which we have found to alter growth and productivity of CHO cells. Understanding the cellular pathways involved in this phenotype might open the way to new strategies for bioprocess-relevant growth regulation.

2:30 Optimization of a Therapeutic Protein Expression Platform

Jianxin Ye, Ph.D., Principal Scientist, Merck Research Labs - Biography 

In order to increase the efficiency of cell line development and improve yield, we have explored optimization of a CHO-based expression system. A combination of different approaches has been explored for this purpose, including host cell adaptation/selection, expression vector design, medium/feed optimization, automated cell culture system, etc. With the combination of these different approaches, an improved CHO expression platform was developed.

3:00 Application of Next-Generation Sequencing and Scale-Down Model on Stable CHO Line Development

Sheng Zhang, Ph.D., Senior Scientist, Process Sciences, Abbvie Bioresearch Center - Biography 

In this case study, we successfully implemented the deep-well scale-down fed batch and the next-generation sequencing of transcriptome throughout the cell line development practice that ultimately led us to the best production clone expressing the correct recombinant mAb. By integrating these two powerful tools in our CLD platform, we demonstrated significantly improved efficiency of clone selection towards greater titer and less risk of product heterogeneity.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing


Transfection 

4:15 The Isolation of CHO Cells Capable of High Transgene Amplification Rates

Jonathan-CacciatoreJonathan Cacciatore, Ph.D., Research Scientist, Chemical Engineering and Biological Sciences, Columbia University - Biography 

A widely used method for isolating Chinese hamster ovary (CHO) cell lines is the selection of clones that have undergone amplification of the transgene coding for the protein. This method is very time consuming and erratic. We employed a method that measures amplification rate at various genomic locations to identify a high-producing clone. We utilized site-specific recombination to target a gene coding for a marker protein into this genomic location and confirmed high gene amplification rate and protein secretion.

4:45 High-Throughput Transfection of Silencing RNA into 3D Cell Cultures

Susan-SharfsteinSusan Sharfstein, Ph.D., Associate Professor, Nanobioscience, Nanoscale Science and Engineering, University at Albany, State University of New York - Biography 

The wealth of genome-sequence information and transcriptomic data generated by sequencing projects and microarray studies, has created a demand for high-throughput methods for annotating gene function. In this talk, I will describe high-throughput approaches for transfecting silencing RNA into culture mammalian cells using novel magnetic nanoparticles and high-throughput viral delivery approaches with an objective of understanding how process conditions affect cell physiology and recombinant protein production in culture mammalian cells.

5:15 Networking Reception with Exhibit & Poster Viewing

6:45 End of Day



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