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Cambridge Healthtech Institute’s 6th Annual
Optimizing Cell Line Development
Enhancing Expression
Part of CHI’s 6th Annual The Bioprocessing Summit

August 21-22, 2014 | Renaissance Waterfront Hotel | Boston, Massachusetts

The “Optimizing Cell Line Development” meeting features experts sharing their case studies and anecdotes that illustrate the strategies they use to reach enhanced expression and lower costs.  Their research and experiences provide meaningful insights into how to best select cell lines and hosts, and develop high-producers into late-stage production.  Gaining a greater understanding of cells through sequencing and the omic sciences will also be addressed, including the CHO genome research, metabolomics, assays, and QPCR.  In addition, challenges for introducing new technologies will be discussed, along with an overview of industrial trends and regulatory perspectives.

Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 

Suggested Short Course*

Bioprocess Development: Considerations for the Quality and Safety of Materials in Contact with Biologics 

Thursday, August 21, 6:30-9:00 pm

*Separate registration required

Thursday, August 21


1:55 pm Chairperson’s Remarks

Jesús Zurdo, Ph.D., Head, Innovation, Biopharma Development, Lonza Biologics plc


Moving Beyond the Off-the-Shelf CHO Host to New Improved Expression Hosts

Scott EstesScott Estes, Ph.D., Director, Cell Culture Development, Biogen Idec, Inc.

CHO does not have a dedicated secretory phenotype and may be ill-equipped to handle the elevated secretory load incurred during the production of biologics. To facilitate a rational selection of candidate targets, we mined published genome wide screens to identify key regulators of secretion. These targets were overexpressed in CHO cells and the resulting engineered hosts studied to determine their ability to express mAbs. Of the fourteen genes investigated, we identified one, a small GTP-binding protein, which significantly improved productivity.

2:45  Evolving to a Rational Bioprocess Model: Applying Lessons from Global Metabolomics of a CHO Process at Lab and Manufacturing Scale

AmandaLanzaAmanda Lanza, Ph.D., Scientist, Bristol Myers Squibb Co.

Traditional Bioprocess development is empirical, requiring a large number of experiments for each cell line and process. The result is both time-consuming and labor intensive. Furthermore, a small number of extracellular metrics are used almost exclusively to make key decisions. Alternatively, an ideal approach would be rationally driven, combining extracellular and systems-level intracellular data to guide Bioprocess development. Here we discuss the application of global, unbiased metabolomics on a CHO cell process at both lab and manufacturing scale, and how these findings can be used to refine the development approach. Finally, we discuss how metabolomics profiles and phenotypes observed at the process level can be used to guide future cell line development.

3:15  Optimization of the CHEF1 CHO Expression Platform

Howard ClarkeHoward Clarke, Ph.D., Director, Upstream Process Development, CMC Biologics

The Chinese Hamster Elongation Factor 1a (CHEF1) platform is designed for the manufacture of recombinant therapeutic proteins in stable CHO cells using chemically defined media. CHEF1 expression has been shown to improve yield over CMV-controlled plasmids in CHO cells and is associated with growth, such that titer increases with volumetric productivity. Recent integration of CMV regulatory domains into the CHEF1 plasmid has led to increased productivity in the later-stage process, increasing production duration and overall yield.

3:45 Sponsored Presentation (Opportunity Available)

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45  Applicability of Readily Grown Mice Cell Lines in Culture for Melanoma Research

Molly Jenkins, Ph.D., Research Fellow, Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine, Dartmouth College

Transgenic mouse models allow the study of melanoma in vivo, however in vitro models are necessary to better understand the molecular mechanisms underlying disease progression and therapy resistance. We have established melanoma cell lines (Dartmouth Murine Mutant Malignant Melanoma; D4M cells) from a conditional mouse model of metastatic melanoma. Here, we report the characterization of these lines, and demonstrate their unique ability to correlate in vitro studies on molecular mechanisms of melanoma with in vivo investigations on pathology and immunology.

5:15  CHippO: Manipulation of the Hippo Signaling Pathway in CHO to Produce a Superior Host for Recombinant Protein Expression

John FollitJohn Follit, Ph.D., Scientist I, Cell Line TechnolMolly Jenkins, Ph.D., Research Fellow, Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine, Dartmouth Collegeogy, Biogen Idec, Inc.

The Hippo signaling pathway controls cell proliferation and organ size by activating Yes-associated protein 1 (Yap1). We hypothesized that altering the Hippo pathway may result in an engineered host cell with an improved bioprocessing phenotype. To this end, we created Yap1 overexpressing CHO cells (CHippO) and auditioned the new host with model monoclonal antibodies. CHippO cells exhibited significant boosts in mAb expression with top clones from the engineering CHIPPO host achieving titers up to three times higher than clones arising from an unmodified host.

5:45 End of Day

5:45-6:30 Dinner Short Course Registration

6:30-9:00 Bioprocess Development: Considerations for the Quality and Safety of Materials in Contact with Biologics *

*Separate registration required

Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 


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