• Scotia Biologics Ltd.

Scotia beyond the bench: Cell Series UK 2019



In October 2019 Dr Alexander Rattray and Dr Catherine Johnson represented Scotia at the Cell Series UK 2019 congress in London. With three diverse programmes (Cell Culture & Bioprocessing, Cell & Gene Therapy and Stem Cell & Regenerative Medicine), 100+ presentations and over 450 attendees from industry and academia it was an ideal opportunity for Scotia to engage with the international scientific community. Alex and Catherine share their highlights of the event.


Evolution of biological tools: Advances in mammalian cell technologies – Dr Alexander Rattray

At Scotia Biologics my primary focus is mammalian protein expression and related process and technology development. The Cell Series UK 2019 congress therefore represented an excellent opportunity to discover and discuss advances in the field with a broad range of therapeutic applications.


A personal highlight of the event was a presentation by Bjørn Voldborg, Director of CHO Cell Line Development at the Technical University of Denmark, detailing the generation of highly engineered CHO cell lines for specific therapeutic applications. Of particular note was the generation of a range of engineered CHO cell lines expressing proteins with defined glycosylation patterns for use as human therapeutics, for example allowing generation of recombinant proteins until now only obtainable from fractionated human plasma such as alpha-1-antitrypsin. With further engineered cell lines in development such as zero lactate, very low ammonia and virus resistant cells it will be exciting to see what their vision of the next generation of CHO cell lines will bring to the field.


Another high point was a presentation by Mike Dyson of IONTAS Ltd detailing their application of mammalian cell display technology as a method for antibody discovery and development. With advances in mammalian library generation by gene editing, and benefits such as authentic post-translational modifications and the potential to screen directly for function in mammalian cells, the continuing improvement of this technology represents an exciting direction for the antibody engineering field.


Stefan Przyborski from Durham University gave an engaging talk detailing his work in the field of 3D mammalian cell culture. Following development of a market-leading membrane scaffold for 3D cell culture, his team have used long-term 3D cell growth and differentiation to develop a range of increasingly complex tissue structure models such as skin, liver and brain. The applications of this technology are varied, from cosmetics testing to in vivo disease modelling in increasingly authentic 3D cellular microenvironments. Of particular note is the application of this technology to model cancer development and potential therapeutics, targets of particular interest to our work here at Scotia Biologics.


Developments in adoptive cell therapies – Dr Catherine Johnson

I joined Scotia Biologics shortly after the company announced an exciting collaboration with TC BioPharm to co-develop novel, tumour-specific single chain antibodies for incorporation into CAR-T cell therapies (chimeric antigen receptor T-cells). Being involved in this project, I was keen to attend the Cell and Gene Therapy stream at the Cell Series UK 2019 congress. Research in this field is rapidly expanding, with several “living drugs” showing promise for the treatment of cancers and other diseases but requiring unique considerations in terms of logistics and manufacture. Reflecting this, wide ranging topics were covered by the speakers. These included research into newer potential cell therapies (e.g. CAR-NK and TAC-T), development of cell therapy delivery systems, encouraging clinical trial results, and design of a training and supply chain portal that bridges the gap between hospitals and the companies that deliver these innovative therapies.


From my perspective, a highlight of the conference was a presentation by Eric Alonso, of the Bluebird bio Cell Analytics team. The team uses mass cytometry, (a technique capable of labelling single cells according to 40+ parameters), to uncover and monitor functionally distinct sub-populations of engineered CAR-T cells during the manufacturing process. Such comprehensive profiling is helping define culture conditions that suppress T-cell exhaustion while enhancing the ratio of T-cells with a memory phenotype, the goal being CAR-T cell infusions that persist longer in the body. Exciting future applications of this technology include biomarker discovery so that correlation between clinical outcome and CAR-T cell composition can be investigated.


Potential drawbacks of clinical-grade genetically engineered cell therapies such as CAR-T however, are that they are expensive and in cases where they recognise a single epitope, can be rendered ineffective in the body through antigen escape. Therefore, a further highlight was a presentation by Mythili Koneru of Marker Therapeutics, who shared encouraging early clinical trial data obtained after administration of Multi-Tumour Associated Antigen T-cells to lymphoma and pancreatic cancer patients. Multi-TAA T-cells are non-engineered T-cells that signal through the native T-cell receptor, making them cheaper to produce. Within the patient T-cell population, tumour-specific T-cells are specifically activated in vitro by dendritic cells primed with a peptide mix covering multiple common tumour antigens. Once expanded, this polyclonal product is infused without the need for lymphodepletion. This, together with their physiological signalling mechanism, is thought to account for the high safety profile of Multi-TAA T-cell therapy with virtually no incidents of cytokine release syndrome. Marker Therapeutics have several on-going clinical trials for haematological and solid tumours so it will be interesting to see how these trials progress.


References

Amann, T., Hansen, A. H., Kol, S., Hansen, H. G., Arnsdorf, J., Nallapareddy, S., Voldborg, B., Min Lee, G., Andersen, M. R., & Kildegaard, H. F. (2019). Glyco-engineered CHO cell lines producing alpha-1-antitrypsin and C1 esterase inhibitor with fully humanized N-glycosylation profiles. Metabolic Engineering, 52, 143-152.

Hill, D.S., Robinson, N.D.P., Caley, M.P., Chen, M., O'Toole, E.A., Armstrong, J.L., Przyborski, S. & Lovat, P.E. (2015). A novel fully-humanised 3D skin equivalent to model early melanoma invasion. Molecular Cancer Therapeutics, 14, 2665-2673.

https://www.markertherapeutics.com/wp-content/uploads/2020/05/TACTOPS-poster-2020-ASCO.pdf

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