Affiliations: [a] Department of Plant Systems Biology, VIB, Ghent, Belgium | [b] Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium
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. RESULT: 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. CONCLUSION: 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.
