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Cambridge Healthtech Institute’s Inaugural

Advances in Vector Production and Scale-Up for Cell and Gene Therapy

Enabling Vector Design, Expression, Development To Meet Commercial Scale Production Demands

January 15-16, 2019



Two autologous CAR T therapies are now on the market, but how will companies manufacture these product at the commercial scale? What technologies and production processes are needed to meet the commercial scale demand? Cambridge Healthtech Institute’s Inaugural Advances in Vector Production and Scale-Up for Cell and Gene Therapy conference will bring together leading scientists from biopharmaceutical industry, academia and government to discuss and showcase innovation in design and engineering of vectors and strategies to overcome production challenges for cell and gene therapy products. Through new presentations, informative panel discussions, high-level poster presentations, and interactive discussions, top scientists will share new insights into various expression systems and production aspects for AAA, Lentivirus, Adenovirus as well as non-viral vector carriers such as nanoparticles, electroporation systems and novel biomaterials.

Final Agenda

 

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TUESDAY, JANUARY 15

1:00 pm Registration (Sapphire West Foyer)

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Trends, Challenges and Opportunities
Sapphire 411

2:00 Chairperson’s Opening Remarks

Sandro Matosevic, PhD, Assistant Professor, Department of Industrial and Physical Pharmacy, Purdue University


KEYNOTE PRESENTATION

2:05 Current Trends and Challenges of Gene Therapy Manufacturing

Palani Palaniappan, PhD, Head, Tech Ops & Andover Site, Sarepta Therapeutics

The keynote will review current status of gene therapy CMC and manufacturing with a view towards future and share Sarepta’s vision in this area. Progress in manufacturing area to align with clinical progression of the pipeline will be highlighted.

2:45 Strategies and Advances in Lentiviral Vector Manufacturing and Scale-Up

Jung_CindyCindy Jung, PhD, Scientific Leader, Vector Process Development, Cell & Gene Therapy Platform CMC, Platform Technology & Science, GSK 

In this presentation, we will discuss strategies and advances in lentiviral vector manufacturing and scale-up such as transient vs. stable cell line approaches, development and optimization of upstream and downstream scalable unit operations, improving process robustness and cost of goods.

3:15 NEW: Addressing Large-Manufacturing of Clinical Grade Viral Vectors Using an Optimized PEI-Based Transfection Process

Géraldine Guérin-Peyrou, Director of Scientific & Technical Support, Polyplus-transfection, France

We describe an optimized PEI-based virus production process for high-yielding viral vector production, compatible with different cell culture adherent and suspension systems. We further demonstrate the robust viral vector production yields, as well as the adaptability and reliability of the PEI-based transient gene expression approach to efficiently manufacture GMP-grade viral vectors at a sufficiently large scale for more advanced clinical trials, and in fine to drive commercialization of therapeutic vectors.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Opportunities for Innovation in Production Processes
Sapphire 400

4:30 Optimizing Sf9-Based Stable Cell Lines for the Production of Highly Infectious rAAV Vectors

Zolotukhin_SergeiSergei Zolotukhin, PhD, Professor, Department of Pediatrics, College of Medicine, University of Florida

We describe a new insect cell-based production platform utilizing attenuated Kozak sequence and a leaky ribosome scanning to achieve a serotype-specific modulation of AAV capsid proteins stoichiometry. By way of example, rAAV5 and rAAV9 were produced and comprehensively characterized side by side with HEK293-derived vectors. The data will be presented demonstrating a superior infectivity and higher genetic identity of OneBac-derived rAAV vectors providing a scalable platform for good manufacturing practice (GMP)-grade vector production.

5:00 LVV Production Process: Recent Advances and Key Challenges

Waghmare_YogeshYogesh Waghmare, PhD, Associate Director, Vector Downstream Process Development, Bluebird Bio

LentiViral Vector (LVV)-based Cell and Gene Therapy products are steadily increasing in number. Industrial production of LVV poses significant challenges compared to AAV due to the large size, complexity, and labile nature of LVV. An overview of industrial LVV production process evolution, recent technological advances, and LVV specific challenges will be presented.

5:30 Close of Day

5:30 - 5:45 Short Course Registration (Sapphire Ballroom)


5:45 - 8:45 Recommended Dinner Short Courses*

SC5: Transient Protein Production in Mammalian Cells - Detailed Agenda

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*Separate registration required

 

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WEDNESDAY, JANUARY 16

7:45 am Registration and Morning Coffee (Sapphire West Foyer)

Vector Design, Development and Characterization for Large-Scale Production
Sapphire 411

8:15 Chairperson’s Remarks

Junghae Suh, PhD, Associate Professor, Bioengineering, Rice University

8:20 Synthetic Virology Approaches to Designing AAV Vectors

Suh_JunghaeJunghae Suh, PhD, Associate Professor, Bioengineering, Rice University

Adeno-associated virus (AAV)-based gene delivery vectors are some of the most promising in the gene therapy field today. To make viral gene delivery a more predictable process, we must obtain control over the naturally encoded biomolecular programs already embedded in the AAV capsids. I will discuss my lab’s work on rewriting the details of what cues can be accepted as input and what functional outputs can be produced by AAV.

8:50 Vector Development and Large-Scale Manufacturing

Jacek LubelskiJacek Lubelski, PhD, Vice President, Global Pharmaceutical Development, uniQure

Scaling up of rAAV manufacturing process displays various challenges, one of which is the variability introduced by starting and raw materials.  I will discuss our effort to limit the sensitivity of uniQure’s rAAV production system to fluctuation in input materials. Furthermore, to exploit the BEVS potential to support large scale rAAV manufacturing I will present our experience with baculoviruses/insect cell system in stirred tank bioreactor and our efforts to make stronger and more specific promoters. Finally, I will discuss the vector quality and potency generated by insect and mammalian cell production systems.

GE_Healthcare 9:20 Bioprocessing of Adenovirus – Technical and Economic Considerations

Lundgren_MatsMats Lundgren, Customer Applications Director, GE Healthcare Life Sciences

Vaccines based on viruses and viral vectors are becoming increasingly important for prevention and the treatment of many diseases. This presentation is focused on manufacturing of Adenovirus (AdV) and the development of an efficient and scalable process for AdV production by evaluation of each process step. Based on analytical data different downstream process alternatives were compared regarding load capacity, recovery and purity and we propose a robust and scalable process with a favorable process economy.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

10:35 Considerations for the Use of Analytical Ultracentrifugation for Characterization and QC Testing of AAV Gene Delivery Vectors

Christopher Sucato, Senior Scientist, Biophysical Characterization, Charles River Laboratories

 

Analytical Ultracentrifugation (AUC) in the biologics has traditionally been employed in the analysis of aggregation and higher order structure, where monomeric protein is commonly the analyte. More recently, the rise of gene delivery vectors to treat pathologies has opened avenues for AUC-based methodologies. Here we explore the parameters of an AUC method which conform to ICH/cGMP validation, and which may remain challenging due to issues inherent with current AUC instrumentation.

 

11:05 Challenges in Viral Vector Manufacture and Analytics

Tristan Thwaites, PhD, Lead Technical Scientist, Industrialization, Cell & Gene Therapy Catapult

The number of viral gene products entering early and late phase clinical trials is significantly on the rise. To meet demand, there is a need to move into scalable and controllable production and purification systems. This presentation will focus on the work at Cell & Gene Therapy Catapult to develop rapid, high-throughput analytical systems to accelerate understanding of the critical process parameters.

11:35 PANEL DISCUSSION: Challenges and Opportunities in Viral and Non- Viral Vector Development and Production

  • New vectors
  • Closing the production gap
  • New production technologies
  • Vector characterization

Moderator:

Sandro Matosevic, PhD, Assistant Professor, Department of Industrial and Physical Pharmacy, Purdue University

Panelists:

Cindy Jung, PhD, Scientific Leader, Vector Process Development, Cell & Gene Therapy Platform CMC, Platform Technology & Science, GSK 

Palani Palaniappan, PhD, Head, Tech Ops & Andover Site, Sarepta Therapeutics

Jacek Lubelski, PhD, Vice President, Global Pharmaceutical Development, uniQure

Christopher Sucato, Senior Scientist, Biophysical Characterization, Charles River Laboratories


12:05 pm Session Break

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break



PLENARY KEYNOTE PANEL (Aqua Salon)

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PepTalk Perspectives: Point-Counterpoint Discussions

2:00 Plenary Keynote Introduction

Norman Packard, PhD, CEO, Daptics


2:10 Plenary Keynote Panel

Moderator:
Howard Levine, PhD, President and CEO, BioProcess Technology Consultants
Panelists:
George BadescuGeorge Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG
Cox ManonManon Cox, PhD, Co-Founder & CEO, NextWaveBio
Zhimei Du, PhD, Director, Bioprocess & Clinical Manufacturing, Merck
Paul Jorjorian, Vice President, BioProcess Sciences, Thermo Fisher Scientific
Marina Kirkitadze, PhD, Deputy Director, Head of Biophysics and Conformation Unit, Analytical R&D Biochemistry, Sanofi Pasteur, Canada
Stefan SchmidtStefan R. Schmidt, PhD, MBA, Head, Operations (COO), BioAtrium AG

 

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

Delivery and Therapy Specific Challenges
Sapphire 411

4:00 Chairperson’s Remarks

Yogesh Waghmare, PhD, Associate Director, Vector Downstream Process Development, Bluebird Bio

4:05 Non-Viral Immunometabolic Reprogramming of Natural Killer Cells for Immunotherapies of Solid Tumors

Matosevic_SandroSandro Matosevic, PhD, Assistant Professor, Department of Industrial and Physical Pharmacy, Purdue University

The anti-tumor immunity of natural killer (NK) cells is highly impaired due to immunometabolic suppression in the microenvironment of solid tumors. For that reason, reprogramming these cells is a therapeutic necessity to enhance their effector function. Here, we discuss the genetic reprogramming of NK cells using non-viral approaches, including recent work focused on imparting new functionality upon NK cells targeting immunometabolism and immune evasion by cancer cells.

4:35 Strategies to Optimize Lentiviral and Retroviral Transduction of NK and T Cells for Adoptive Immunotherapy

Alici_EvrenEvren Alici, MD, PhD, Assistant Professor of Hematology, Karolinska Institutet, Department of Medicine, Stockholm, Sweden

In order to manufacture more efficient NK cell therapy products, it is essential to develop novel strategies such as genetic modification of NK cells. The introduction of either activating or chimeric antigen receptors customized for NK cells presents an attractive prospect for further clinical applications. Although NK cells are inherently resistant to retroviral and lentiviral transductions, recently, our group has significantly enhanced retroviral and lentiviral gene delivery to NK cells through enhanced proliferation and targeting intracellular viral defense mechanism by small molecule inhibitors.

5:05 Breakout Discussions

Join the moderated discussions to share ideas, gain insights, establish collaborations, or commiserate about persistent challenges. Then continue the discussion as you head into the lively Exhibit Hall.

Topic: Different Flavors Of Vectors And What Does It Mean?

Moderator: Yogesh Waghmare, PhD, Associate Director, Vector Downstream Process Development, Bluebird Bio

  • For Gene Therapy product vector is the product and for Cell therapy products, vector is starting material. How does this difference practically translate into:
  • Regulatory strategy
  • Target quality profile
  • Process development goals etc.

Topic: Cell-Based Immunotherapies for Solid Tumors: Are We There Yet?

Moderator: Sandro Matosevic, PhD, Assistant Professor, Department of Industrial and Physical Pharmacy, Purdue University

  • Tumor microenvironment immunosuppression: not like hematological malignancies
  • Cell engineering for tumor homing and persistence
  • Vector design considerations to enhance immune cell cytotoxicity

Topic: Gene Therapy Validation and Commercialization

Moderator: Tristan Thwaites, PhD, Lead Technical Scientist, Industrialization, Cell & Gene Therapy Catapult


  • Quality by Design
  • Gene therapy analytics and characterization
  • Process qualification and validation

6:05 - 7:00 Networking Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)

7:00 Close of Advances in Vector Production and Scale-Up for Cell and Gene Therapy Conference


Day 1 | Day 2 | Download Brochure