title: Plant expression systems for early stage discovery and development of lead therapeutic antibodies.
abstract: BACKGROUND
  Antibodies for human clinical applications are predominantly produced in mammalian expression systems, with Chinese hamster ovary (CHO) cells being the gold standard. CHO cells are ideal for the manufacturing of the IgG class of antibodies, but not for the production of complex antibodies like secretory IgAs (SIgAs) and IgMs, which remain unavailable for clinical use. In contrast, plant seeds and leaves hold the promise to produce SIgAs, IgMs and similar complex antibody formats to scalable amounts. Using transient transformation of Nicotiana benthamiana leaves, complex antibody formats can be produced up to milligram amounts in less than a month.
  
  
  OBJECTIVE
  Based on these merits, we propose a model for early-phase exploration and designing of innovative antibody formats for therapeutic application. Further in this essay, we elaborate how the model was followed during the selection of novel antibodies for seed-based production.
  
  
  RESULTS
  This exploratory model led to the engineering of novel light-chain devoid porcinized-llama antibodies (VHH-Fc) of the IgG (VHH-IgG) and IgA (VHH-IgA) isotypes and also tetravalent dimeric and SIgAs.
  
  
  CONCLUSIONS
  The proposed strategy may lead to plant-based rapid engineering of innovative antibodies more apt and efficacious for therapy, and in the coarse also add to the understanding of their mode of action.
authors.affiliation: Department of Plant Systems Biology, VIB, Ghent, Belgium.|Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Vikram
authors.initials: V
authors.lastname: Virdi
authors.affiliation: Department of Plant Systems Biology, VIB, Ghent, Belgium.|Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Paloma
authors.initials: P
authors.lastname: Juarez
authors.affiliation: Department of Plant Systems Biology, VIB, Ghent, Belgium.|Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Depicker
mesh_terms: D017360:Arabidopsis / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D018515:Plant Leaves / Q000235:genetics / Q000378:metabolism; D030821:Plants, Genetically Modified; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012639:Seeds / Q000235:genetics / Q000378:metabolism; D014026:Nicotiana / Q000235:genetics* / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D011994:Recombinant Proteins
keywords: First-in-plants; antibody engineering; edible antibodies; innovative antibodies; scalable antibody production; secretory IgA