Title

Moving Beyond CHO: Alternative host systems may be the future of biotherapeutics

Conference Dates

May 6-11, 2018

Abstract

CHO cells are the primary expression system for recombinant proteins with significant investment over the last three decades resulting in robust cell lines and processes. The flexible nature of CHO has lent itself to multiple process formats, such as fed batch, perfusion and continuous cultures, and advances in omics technology has enabled customization of media formulations and targeted engineering of CHO cells. This knowledge has led to large gains in protein productivity that can be captured with culture duration and/or scale. Despite this, constant pressure exists to reduce cost of manufacturing and improve per batch productivity to meet the needs of increased patient populations and increase accessibility of these therapeutics. Biogen has partnered with MIT to take a holistic view of the potential future of biomanufacturing to identify technologies that can make step changes in productivity and cost reduction. This effort has identified the host system as the most important factor to enabling this vision. Specifically, a non-mammalian host could be the key to realizing the most significant gains in productivity and reduction in cost of manufacturing. Through this initiative, we sought to take a more comprehensive approach to investigate alternative hosts for recombinant antibody production. Eight non-mammalian hosts were selected based on several properties, including proven secretion of recombinant protein products, ability to glycosylate proteins, established genome or molecular biology toolkit, amongst others. The final panel of organisms included yeast, filamentous fungi, a diatom, and a trypanosome. In collaboration with Amyris, we evaluated these eight non-mammalian host cell lines to compare their suitability as a potential primary host for the biotechnology industry. Only non-engineered, wild-type strains were used as a starting point for this evaluation, which assessed the ability of each host to express the same IgG1 model antibody. The outcome of this comparative analysis demonstrated that several of the alternative hosts could express full length antibody with acceptable glycoforms. Additionally, the ease of culture, ability to engineer the genome, and flexibility of carbon source were assessed. As an output of this work, the most productive strains will be made available for use without restrictions to allow others in the community to freely work with these hosts. Based on this initial assessment, a strategy to further investigate the potential of the most promising hosts will be shared.

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