The use ofDrosophilaS2 cells in R&D and bioprocessing

Abstract

Drosophila Schneider 2 (S2) cells have been available for approximately 40 years. Their use has intensified over the past 15 years: resolution of the whole Drosophila melanogaster genome and the amenability of S2 cells for siRNA-based studies are some of the reasons for their growing use. This review covers recent publications on use of S2 cells for research and manufacturing and points to some possible future developments in their use in the vaccine field. Relatively few groups have systematically developed the system to enable expression of challenging proteins. They demonstrated that these cells can constitute a robust, efficient protein expression system, with specific advantages such as homogeneous glycosylation profile; reproducibility between production runs; options for cultivation modes, including perfusion; and no cell lysis, leading to relatively low levels of contaminating host cell proteins. The platform has shown to be particularly well adapted for the production of challenging viral, malaria and immunotherapy antigens.

Expression, Purification, and Characterization of Bovine Leukemia Virus-Like Particles Produced in Drosophila S2 Cells

“…VLPs are produced in different cellular systems, including yeast, bacteria, mammalian, plants, and insect cells (24)(25)(26). Drosophila melanogaster Schneider (S2) cells have been used in the efficient production of several VLP types (27)(28)(29)(30). S2 cells display several advantages as a eukaryotic system for protein expression: simple glycosylation profiles, fast-growing in a serum-free medium, very high cell densities without aggregation or toxic metabolite issues, and lack of adventitious agents that could infect humans (27).…”

Optimized expression of the antimicrobial protein Gloverin from Galleria mellonella using stably transformed Drosophila melanogaster S2 cells

“…Insect cells should be ideal for the expression of Gloverins because they closely resemble the natural AMP-producing tissue in terms of protein folding and pro-peptide cleavage, and are unlikely to be susceptible to AMP toxicity. In this context, stable recombinant Drosophila melanogaster S2 cells (rS2 cells) provide an effective system for protein expression (Moraes et al 2012;de Jongh et al 2013) and these cells are particularly suitable for the production of biologically active small peptides, such as spider toxins (Escoubas et al 2003) and insect AMPs. Accordingly Manduca sexta and Plutella xylostella Gloverins have already been expressed successfully in rS2 cells (Xu et al 2012(Xu et al , 2015.…”

FAS2FURIOUS: Moderate-Throughput Secreted Expression of Difficult Recombinant Proteins in Drosophila S2 Cells

“…S2 cells are capable of complex eukaryotic posttranslational modifications, including mostly paucimannosidic N-linked glycosylation ( Vandenborre et al, 2011 ). S2 cells are “powerhouse” protein secretors, with recombinant protein yields >30 mg/L allowing industrial-scale production of challenging proteins, including a malaria vaccine, West Nile virus vaccine, HER-2 vaccine, virus-like particles, and antibodies ( Adriaan de Jongh et al, 2013 ). S2-derived proteins led to the deposition of more than 60 structures into the PDB, including receptor ectodomains, viral glycoproteins, enzymes, hormones, and growth factors.…”

“…S2-derived proteins led to the deposition of more than 60 structures into the PDB, including receptor ectodomains, viral glycoproteins, enzymes, hormones, and growth factors. Interested readers are directed to excellent reviews which cover the details of S2 systems ( Moraes et al, 2012 ; Adriaan de Jongh et al, 2013 ; Zitzmann et al, 2017 ).…”