title: Developments in the production of mucosal antibodies in plants.
abstract: Recombinant mucosal antibodies represent attractive target molecules for the development of next generation biopharmaceuticals for passive immunization against various infectious diseases and treatment of patients suffering from mucosal antibody deficiencies. As these polymeric antibodies require complex post-translational modifications and correct subunit assembly, they are considered as difficult-to-produce recombinant proteins. Beside the traditional, mammalian-based production platforms, plants are emerging as alternative expression hosts for this type of complex macromolecule. Plant cells are able to produce high-quality mucosal antibodies as shown by the successful expression of the secretory immunoglobulins A (IgA) and M (IgM) in various antibody formats in different plant species including tobacco and its close relative Nicotiana benthamiana, maize, tomato and Arabidopsis thaliana. Importantly for biotherapeutic application, transgenic plants are capable of synthesizing functional IgA and IgM molecules with biological activity and safety profiles comparable with their native mammalian counterparts. This article reviews the structure and function of mucosal IgA and IgM antibodies and summarizes the current knowledge of their production and processing in plant host systems. Specific emphasis is given to consideration of intracellular transport processes as these affect assembly of the mature immunoglobulins, their secretion rates, proteolysis/degradation and glycosylation patterns. Furthermore, this review provides an outline of glycoengineering efforts that have been undertaken so far to produce antibodies with homogenous human-like glycan decoration. We believe that the continued development of our understanding of the plant cellular machinery related to the heterologous expression of immunoglobulins will further improve the production levels, quality and control of post-translational modifications that are 'human-like' from plant systems and enhance the prospects for the regulatory approval of such molecules leading to the commercial exploitation of plant-derived mucosal antibodies.
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Plant Biotechnology, Forckenbeckstrasse 6, 52074 Aachen, Germany.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Vasilev
authors.affiliation: School of Biosciences, University of Kent, CT2 7NJ Kent, UK.
authors.forename: C Mark
authors.initials: CM
authors.lastname: Smales
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Plant Biotechnology, Forckenbeckstrasse 6, 52074 Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schillberg
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Plant Biotechnology, Forckenbeckstrasse 6, 52074 Aachen, Germany; RWTH Aachen University, Institute for Molecular Biotechnology, Worringerweg 1, 52074 Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Plant Biotechnology, Forckenbeckstrasse 6, 52074 Aachen, Germany. Electronic address: andreas.schiermeyer@ime.fraunhofer.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schiermeyer
mesh_terms: D000906:Antibodies / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017360:Arabidopsis; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014026:Nicotiana; D003313:Zea mays
chemical_list: D000906:Antibodies; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D011994:Recombinant Proteins
keywords: Biopharmaceuticals; Immunoglobulin A; Immunoglobulin M; Plant glycoengineering; Plant-made recombinant proteins; Secretory antibodies; Transgenic plants