Challenging the workhorse: Comparative analysis of eukaryotic micro‐organisms for expressing monoclonal antibodies

Abstract

For commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture. For CHO‐based manufacturing, achieving this combination of targeted improvements presents challenges. Based on a holistic analysis, the choice of host cells was identified as the single most influential factor for both increasing productivity and decreasing costs. Here we evaluated eight wild‐type eukaryotic micro‐organisms with prior histories of recombinant protein expression. The evaluation focused on assessing the potential of each host, and their corresponding phyla, with respect to key attributes relevant for manufacturing, namely (a) growth rates in industry‐relevant media, (b) adaptability to modern techniques for genome editing, and (c) initial characterization of product quality. These characterizations showed that multiple organisms may be suitable for production with appropriate engineering and development and highlighted that yeast in general present advantages for rapid genome engineering and development cycles.

Comparative genome‐scale analysis of Pichia pastoris variants informs selection of an optimal base strain

“…Rapidly advancing technologies for genomic engineering of hosts are promoting renewed consideration of microbial hosts for these tasks (Wagner & Alper, ). Selection of an optimal host for pursuing such purposes, however, can be difficult: many organisms may be suitable hosts, and for each organism, several variants typically exist (Jiang et al, ; Matthews et al, ). A framework for the rational evaluation of potential hosts could further promote the adoption of alternative hosts for commercial protein expression.…”

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

“…In a recent study, eight wild-type eukaryotic micro-organisms (including yeast, filamentous fungi, and mammalian cells) were evaluated to assess growth rates in industry-relevant media, adaptability for genome editing, and product quality. This study showed that multiple organisms may be suitable for recombinant protein production with appropriate engineering and development and highlighted the advantages of yeast for rapid genome engineering and development cycles (Jiang H. et al, 2019).…”

Engineering monoclonal antibody-based contraception and multipurpose prevention technologies†

“…These proteins are typically enzymes for industrial purposes (e.g., detergents) but may be adaptable to production of pharmaceutical-grade antibodies, especially for topical use. Some yeast (e.g., Pichia pastoris ) and fungus (e.g., Trichoderma reesei ) have been evaluated for production of antibodies [ 42 , 43 ] that could address the metric ton challenge for antibodies. In addition to a quality expression host, the perspective of regulatory agencies on utilization of existing infrastructure (e.g., 300,000 L fermenters) for manufacturing topical contraceptive antibodies may be crucial in avoiding enormous capital costs.…”