The 26th ESACT conference, ESACT 2019, took place in Copenhagen (Denmark) on May 5–8 2019. It was organized by the European Society for Animal Cell Technology (ESACT), the leading European not-for-profit society in this scientific field. More than 1000 delegates from 35 countries met in Copenhagen to discuss scientific topics related to academic and industrial research and development on animal cell technology.
The oral program had 10 sessions on topics spanning from cell engineering and omics, to novel technologies for gene and cell therapeutics development, cell culture process engineering and integration with downstream purification to advances in cell culture process controls and analytics. The program was kicked off by a very inspiring Inaugural Innovation Award Lecture given by the very first ESACT Innovation Award winner, Volker Sandig (Germany), and included two top-class keynote lectures given by Peter Zandstra (Canada) and Mathias Uhlen (Sweden), on stem cells fate and on the human secretome project, respectively. During three lively poster sessions more than 350 posters were presented and discussed while the hard-working poster jury selected the top 3 posters to be awarded with the poster prizes. As always at ESACT, the conference also hosted a very large exhibition area where all the latest news in cell culture equipment, analytical instruments, cell culture media and animal cell technology know-how were made available to the delegates by many supplier companies. On top, 10 academic and company workshops were given prior to the official opening of ESACT2019.
The >1000 conference ESACT 2019 delegates came from all over the world representing no less than six continents and 35 countries. An important mission of ESACT is to provide opportunities for young scientists to attend conferences and give scientific presentations. This time, ESACT 2019 proudly granted bursaries to more than 65 students from around the globe, allowing these young people to travel to Copenhagen and present their work at a top scientific conference for a large audience.
This year, the ESACT meeting started off with an exciting novelty: The ESACT Innovation Lecture, which was presented by the first Award winner, Volker Sandig (ProBioGen; Berlin, Germany). Sandig has been a very active and inspiring scientific leader in the animal cell technology area and his work has frequently been presented at former ESACT meetings. His lecture entitled “Cell Engineering – a small step for the biotechnologist, a leap for the application?” took us through his impressive scientific career with examples of the many innovations he has made to keep improving mammalian cells for them to better serve development of biotherapeutics, vaccines and other cell culture-derived products, for example the GlymaxX technology, which enables production of recombinant antibodies with highly improved bioactivity against cancer cells via enhanced antibody-dependent cellular cytotoxicity.
The scientific program was structured around 5 overall topics: Cell engineering, novel technologies and omics; Cell culture process controls and analytics; Use of viral- and non-viral vectors for generating new gene therapeutic products and vaccines;, Cell culture process engineering product quality and integration of downstream processing; and development of cell-based technologies and therapeutics.
These were purposefully mixed and distributed throughout the 4 conference days, to allow inspiration and cross-fertilization of technological insights from the “old” biotherapeutics and bioprocessing fields, based on recombinant proteins, with the younger but strongly growing areas of gene and cell therapy that use either naked DNA/RNA, viral vectors or entire cells of autologous or allogeneic origin for human therapy. Both manufacturing concepts, as well as process controls and analytical methods used in the different fields, may well be leveraged by colleague researchers in sister fields.
Cell engineering, novel technologies and omics
While most speakers were selected based on ranking by the scientific committee of the almost 400 abstracts received, the program also comprised invited speakers who have had strong influence and progressed the scientific field into novel directions. One of the invited speakers, Ron Weiss (MIT; MA, USA) opened the first session on cell engineering, novel technologies and omics, sharing his passion for synthetic biology with an impressed audience, showing his group’s continuous attempts to use synthetic elements to better control and structure standard yet difficult-to-control cellular processes like glycosylation and mRNA expression.
Veronique Chotteau (KTH; Stockholm, Sweden), who has many years of experience in the currently very “hot” perfusion technology, presented omics data including, importantly, how to structure these in databases for easy application – with the purpose to understand and possibly circumvent negative molecular processes underlying high cell-density and/or shear-induced stress conditions that can occur in perfusion cultures, exemplified here by changes in expression of proteins associated with cytoskeleton.
To complement the longer scientific presentations, 5-minute Poster Spotlight talks were again spread out in the various sessions. These beloved short talks were delivered by very well-prepared authors in an energetic and concise manner, inspiring the audience to visit the presented posters later.
Cell culture process controls and analytics
Mike Betenbaugh (Johns Hopkins Institute; MD, USA) opened the process controls and analytics topic by discussing amino acid metabolic profiling in CHO cells, and he also shared information about the Advanced Mammalian Biomanufacturing Innovation Center .
Iris Bodenmann (Selexis; Plan-les-Ouates, Switzerland) gave a user perspective on the Beacon instrument, which can be used both to characterize cells at the single-cell level and also to support cloning during cell line development. The instrument, which is sold by Berkeley Lights (CA, USA), who also gave a workshop on their technology at the conference, is becoming increasingly popular in the industry due to its advanced liquid handling, optics and analytical features.
Jette Wypych (Amgen; CA, USA) told the audience about the considerable efforts taken by Amgen not only to develop the smart, fast and precise analytical concept known as Multi-Attribute Mass (MAM) Spectrometry, but also to work with regulatory authorities to gain confidence in this novel approach and obtain acceptance of the use of this type of data for regulatory filings including market applications. This has been a long journey that has developed positively but still has a few miles to go before the first molecule characterized by MAM can get on the market.
Use of viral and non-viral vectors for generating new gene therapeutic products and vaccines
The ESACT 2019 program included two sessions addressing the growing field of gene therapy, and this year the focus of the invited and selected talks was on the manufacturing challenges and solutions currently experienced by those developing new therapeutics in this field. Lesley Chan from bluebird bio (MA, USA), and Joana Boura from Oxford BioMedica (Oxford, UK) both spoke on the need to develop faster and more scalable lentiviral vector (LV) production processes, with Boura opting for the benefits of creating a safe, universal ready-to-use producer cell line. Suspension culture, which is more readily scalable, is another big wish. The other most commonly used virus type in the gene therapy field is the adeno-associated virus (AAV), and similar scalability issues as for the lentiviral vector manufacturing were addressed by Bethany Kerr (CPI; UK) in her talk on scalable transfection conditions for AAV production. Ana Sofia Coroadinha (iBET; Portugal) presented important progress in the LV packaging cell field, reporting replacement of the versatile but toxic VSV-G envelope protein with non-toxic molecules.
Robert Baffi (BioMarin; CA, USA), presented a great overview of the CMC challenges associated with bringing these advanced therapeutics to market, and elegantly showed how learnings from the more mature field of protein biotherapeutics can be leveraged here. It was clear from both his and other presentations that the manufacturing suppliers in the cell and gene therapy space are not nearly as available – or experienced – compared to manufacturers in the protein modality space.
Cell culture process engineering, product quality and integration of downstream processing
In-line with the significant improvements in perfusion and continuous processing in recent years, the process engineering session talks were this year selected with a special focus on continuous processing and integration of upstream and downstream processing.
Jeff Salm, (Pfizer, NY, USA), kicked off the topic giving a great lecture on the “Benefits of the fully integrated bioprocess” where he described long-standing collaborative efforts between Pfizer and Boehringer-Ingelheim (Germany) to develop a robust, implementable and high-titered continuous processing format based on a relatively short (14 days) upstream perfusion process combined with continuous capture and virus inactivation steps, while keeping final DSP steps like the UF/DF steps as simple batch unit operations. The approach focused very much on ease of development and operation, and impressive outputs of 15–60 kg per batch with an average production rate of 1-4 g/L/day were shown, even peak productivities of 5–6 g/L/day on later days of the production runs. Other large biopharma companies, including Amgen and Merck Serono also presented on perfusion and continuous processing, Amgen on a program where the molecule stability demanded short incubation time in the bioreactor, while Jean-Marc Bielser (Merck Serono; Switzerland) presented his company’s broad attempt to install continuous processing, including perfusion, as a standard manufacturing platform enabling smaller footprints and lower investment costs when establishing new good manufacturing practice GMP manufacturing capacity. A hallmark of these huge undertakings was that they often involve strong collaborative efforts, either between companies or with academia as in the Merck Serono case, where ETH Zurich (Switzerland) had been a strong collaborator.
Development of cell-based technologies and therapeutics
The first session on cell therapy was kicked-off by Nick Timmins (BlueRock Therapeutics; ON, Canada), who spoke about Bluerock’s efforts to establish a universal pluripotent master cell bank derived from induced pluripotent stem cells (iPSCs) for use both in the cell and gene therapy areas.
Another great talk on the manufacturing challenges – and their potential solutions – was given by Uwe Gottschalk (Lonza: Switzerland), who described Lonza’s approach to build small “cocoon” incubators dedicated to accommodate the growing GMP manufacturing challenge experienced with these often individualized cell and gene therapies, which have extreme requirements compared to traditional biotherapeutics both in terms of speed – time from cells are collected from the patient until they should be back – raw material usage and scaling up. Several speakers discussed development and/or modeling of specific cell types to be used either for drug discovery, as exemplified by Catarina Brito (iBET, ) in her talk entitled “A flexible 3D human hepatitic cell platform for malaria drug discovery” and by Dagmar Wirth (Helmholtz Centre for Infection Research; Braunschweig, Germany) in her talk “A 3D Kaposis sarcoma herpesvirus (KSHV) latency model for identification of antiviral compounds” or with the attempt to ultimately serve patients with failing organs in the field of regenerative medicine and tissue engineering, such as was presented by Ioannis Papantoniou (Universite de Liege; Belgium) in his talk “Bone by design – via bio assemblies of cartilage microtissue modules” and by Maria Sebastiao (iBET) in her talk “In vitro models to disclose human cardiac progenitor cells action mode”.
ESACT Frontiers is a group of younger scientists working in the animal cell culture field. They contribute to the biannual ESACT meetings in many ways and have also started to arrange their own ESACT Frontiers meetings. The winner of the oral presentation prize at the second ESACT Frontiers Congress held in Zagreb, Croatia in 2018, Nikolas Zeh (University of Applied Sciences Biberach, Germany), was invited to present his award lecture on exosomes for targeted delivery of microRNAs. His presentation was much appreciated, and so were the multitude of other conference contributions by the ESACT Frontiers. This year, the Frontiers had organized an interesting workshop on Design Thinking, moderated by Guilherme Martins Vitorino, (NOVA IMS; Portugal) – which included innovative model building appropriately facilitated by the Danish product Lego. Furthermore, the Frontiers again this year took responsibility to organize the Poster Award competition that involved no less than 30 Poster Jury members judging the 100 posters originally rated highest during the abstract review by the Scientific Committee. Ricardo Valdes-Bango Curell (National Institute for Cellular Biotechnology; Dublin, Ireland) and Nusa Pristovsek (Technical University of Denmark, Denmark) headed the committee and proudly announced the winners at the conference closing ceremony.
1st prize: Daniel Arturo Zavala Ortiz, Instituto Tecnologico de Veracruz, Mexico and University de Lorraine, France: Chemometrics to Monitor CHO Cells cultures Quality by in situ NIRs
2nd prize: Bhanu Chandra Mulukutla, Cell Culture Process Development, Pfizer, USA: Metabolic Engineering to Reduce Growth Inhibitory Byproducts
3rd prize: Iván Martínez-Monge, The Novo Nordisk Foundation Center for Biosustainability, DTU, Denmark: Lactate Reduction in CHO Cell Cultures Through the Metabolic Analysis
Per tradition, ESACT is not only about scientific sessions; networking and cultural experiences are always offered as a very important part of the conference. This year, the social program included a self-guided walking tour in groups through historical Copenhagen, with pit-stops included where typical Danish culinary surprises were offered, a dinner in the world-famous amusement park Tivoli as well as a canal boat tour ending at the site of the Congress dinner which always closes the ESACT meeting and which again this year was attended by more than 700 delegates. As in previous years, the dance floor was packed with people having fun together after 4 days of intense animal cell culture focus.